摘要
老年人和老年动物常表现出运动平衡障碍、运动不协调和力量减弱,这些运动相关行为的变化是衰老的标志之一。在正常衰老过程中,参与运动调控的黑质-纹状体多巴胺能神经元发生退行性改变,表现为反映多巴胺(dopamine,DA)能神经元功能活动的两大标志物酪氨酸羟化酶(tyrosinehydroxylase, TH)和多巴胺转运体(dopamine transportet, DAT)的表达减弱。黑质-纹状体DA能神经元功能活动的减弱显著影响老年机体的运动相关行为。
研究显示,雄性甾体激素(anabolic androgenic steroids,AAS)能够影响机体的行为,改变中枢DA能神经元的功能状态。AAS增加老年雄性小鼠的抗焦虑行为和认知行为、改变成年大鼠探索行为等多个旷场行为指标、增强雄性大鼠脑内DA的代谢,补充睾酮逆转去势引起的雄性大鼠纹状体TH活性的降低。
胶质细胞源性神经生长因子可以提高老年大鼠黑质和纹状体的TH活性、增强老年大鼠的运动能力,暗示外源性干预因素可以作用于老年大鼠黑质-纹状体DA能神经元并影响老年大鼠的运动行为。研究发现老年雄性大鼠血清睾酮水平的显著降低,补充睾酮可提高老年大鼠内侧视前区的DA能神经元的活动,维持其正常的性活动。补充雄激素能否改变老年雄性大鼠黑质-纹状体DA能神经元的功能活动,从而改善其运动相关行为的障碍目前尚不清楚。临床资料显示睾酮参与帕金森病(Parkinson’s disease,PD)的神经病理生理改变,伴有睾酮缺乏的帕金森病患者在睾酮替代治疗后,静止性震颤、精细运动调控和非运动症状均得到显著改善,而且运动症状的改善程度与血清睾酮水平的升高有关。我们推测对老年雄性大鼠给予睾酮处理可能会提高黑质-纹状体DA能神经元的功能状态,从而改善老年雄性大鼠的运动相关行为。
因此,本研究利用旷场实验、倾斜面实验、水平绳实验和粘附物去除实验,分析丙酸睾酮(testosterone propionate, TP)处理对老年大鼠运动相关行为的影响;通过免疫细胞化学、免疫印迹以及RT-PCR技术观察TP处理后老年雄性大鼠黑质-纹状体TH和DAT的表达变化;通过细胞培养分析睾酮(testosterone, T)处理后SH-SY5Y细胞TH和DAT的表达,推测雄激素改善老年大鼠黑质-纹状体DA能神经元功能状态的可能机制,期望所获结果为以雄激素替代辅助治疗老年运动相关行为障碍提供一定的实验依据。
第一部分:丙酸睾酮改善老年雄性大鼠的运动相关行为
目的:探讨TP处理对老年雄性大鼠运动相关行为的影响。
方法:通过旷场实验、倾斜面实验、水平绳实验和粘附物去除实验观察TP处理后老年雄性大鼠运动相关行为的变化,放射免疫分析法检测TP处理后老年雄性大鼠血清睾酮含量的变化。
结果:
1.通过旷场实验发现,24Mon组老年大鼠的静止闻嗅次数,Walking、Climbing、Rearing、Sniffing次数,垂直运动和水平运动次数,总径长,理毛次数和理毛持续时间比6Mon组分别降低了39%(P<0.01)、52%(P<0.01)、39%(P<0.01)、69%(P<0.01)、51%(P<0.01)、50%(P<0.01)、56%(P<0.01)、55%(P<0.01)、59%(P<0.01)和55%(P<0.01),理毛潜伏期比6Mon组延长了392%(P<0.01);长期TP处理后,老年大鼠的静止闻嗅次数,Climbing、Rearing、Sniffing次数,垂直运动次数比24Mon组分别升高了27%(P<0.05)、37%(P<0.05)、97%(P<0.01)、44%(P<0.05)和52%(P<0.05),差异显著;其中Climbing次数恢复至6Mon组水平。
2.通过倾斜面实验发现,24Mon组老年大鼠的倾斜面下滑角度比6Mon组降低了22%(P<0.01),50°夹角滑下次数增加了550%(P<0.01);长期TP处理后,老年大鼠的倾斜面下滑角度显著增加(P<0.05),50°夹角滑下次数显著减少(P<0.01)。
3.通过水平绳实验发现,24Mon组老年大鼠的悬挂时间比6Mon组大鼠缩短了62%(P<0.01);长期TP处理后,老年大鼠的悬挂时间比24Mon组明显延长(P<0.01)。
4.通过粘附物去除实验发现,24Mon组老年大鼠的左鼻和右鼻粘附物去除时间比6Mon组大鼠分别延长了382%(P<0.01)和577%(P<0.01),左前爪和右前爪粘附物去除时间比6Mon组分别延长了1410%(P<0.01)和1156%(P<0.01);长期TP处理后,老年大鼠的左鼻(P<0.05)、右鼻(P<0.05)和左前爪(P<0.01)、右前爪(P<0.01)粘附物去除时间均显著降低,但仍与6Mon组水平有显著差异。
5.24Mon组大鼠的血清睾酮含量比6Mon组降低了61%(P<0.05),TP处理使老年大鼠血清睾酮水平显著升高(P<0.01)。
结论:
1.24月龄老年雄性大鼠的旷场运动行为显著低于6月龄大鼠;长期TP处理可以改善老年大鼠的旷场运动行为。
2.24月龄老年雄性大鼠平衡反应能力、肌张力和运动协调能力比6月龄大鼠显著降低;长期TP处理可以改善这些受损的运动技能。
3. TP处理可以显著升高老年雄性大鼠血清睾酮水平。
第二部分:丙酸睾酮增强老年雄性大鼠黑质-纹状体DA能神经元TH和DAT的表达
目的:探讨丙酸睾酮处理对老年雄性大鼠黑质-纹状体DA能神经元TH和DAT表达的影响。
方法:通过免疫细胞化学和免疫印记检测TH和DAT在老年雄性大鼠黑质和尾壳核的表达。
结果:
1.免疫细胞化学实验发现:24Mon组老年大鼠SN的TH表达比6Mon组降低了25%(P<0.01),CPu的TH表达比6Mon组降低了28%(P<0.01),长期TP处理后SN和CPu的TH表达分别升高了14%(P<0.01)和26%(P<0.01),差异显著。24Mon组老年大鼠SN和CPu的DAT表达比6Mon组分别降低了22%(P<0.01)和32%(P<0.01),TP处理使SN(P<0.01)和CPu(P<0.05)的DAT表达显著升高,其中24Mon-TP组大鼠SN的DAT表达恢复到了6Mon组水平。
2.免疫印记实验发现:24Mon组老年大鼠SN和CPu的TH表达分别比6Mon组降低了28%(P<0.01)和36%(P<0.01),长期TP处理后SN和CPu的TH相对表达分别升高了22%(P<0.01)和68%(P<0.01),CPu的TH表达恢复至6Mon组水平。24Mon组老年大鼠SN的Glyco-DAT的相对表达比6Mon降低了54%(P<0.01),Non-Glyco-DAT降低了26%(P<0.05);CPu的Glyco-DAT相对表达比6Mon组降低了71%(P<0.01),Non-Glyco-DAT降低了39%(P<0.01);TP处理后,老年大鼠SN和CPu的Glyco-DAT、CPu的Non-Glyco-DAT的相对表达分别升高了74%(P<0.01)、89%(P<0.01)和35%(P<0.05),SN的Non-Glyco-DAT的相对表达没有显著变化。
结论:
1.24月龄老年雄性大鼠SN和CPu多巴胺能神经元TH的表达明显降低;长期给予TP能够显著增加老年雄性大鼠SN和CPu的TH表达。
2.24月龄老年雄性大鼠SN和CPu糖基化与非糖基化DAT的表达均显著降低;长期TP处理可显著升高SN糖基化DAT、CPu的糖基化和非糖基化DAT的表达,而对SN非糖基化DAT表达没有显著影响,说明TP可能影响DAT的糖基化过程。
第三部分:丙酸睾酮增强老年雄性大鼠黑质-纹状体DA能神经元THmRNA和DAT mRNA的表达
目的:探讨丙酸睾酮在转录水平对老年雄性大鼠黑质-纹状体DA能神经元的影响。
方法:通过RNA提取、RT-PCR检测丙酸睾酮处理后老年雄性大鼠黑质TH mRNA和DAT mRNA的表达。
结果:与6Mon组大鼠相比,24Mon组大鼠SN的TH mRNA(P<0.01)和DAT mRNA(P<0.01)的表达都显著下降;长期TP处理使老年雄性大鼠黑质TH mRNA和DAT mRNA表达显著升高,恢复至6Mon组水平。
结论:长期TP处理升高老年雄性大鼠黑质TH mRNA和DAT mRNA的表达,表明TP可以转录水平影响黑质-纹状体DA能神经元TH和DAT的表达。
第四部分:睾酮对分化的SH-SY5Y细胞TH和DAT表达的影响
目的:探讨睾酮对分化的SH-SY5Y细胞DA能神经元功能状态的影响。
方法:RA/TPA诱导SH-SY5Y细胞分化6天,通过免疫印迹、RT-PCR检测睾酮处理对RA/TPA分化的SH-SY5Y细胞TH和DAT表达的影响。
结果:
1. RA/TPA分化6天后,SH-SY5Y细胞形态发生显著变化,突起明显增多、变长,细胞NeuN表达增加。
2.台盼蓝活细胞计数和MTT检测均显示10nM和100nM T处理24小时和48小时对细胞活性没有显著影响。
3.免疫印迹结果显示,与Con-24h组细胞相比,10nM-24h组RA/TPA分化的SH-SY5Y细胞TH的表达升高了123%(P<0.01),100nM-24h组分化细胞TH的表达降低了58%(P<0.01);与Con-48h组细胞相比,10nM-48h组RA/TPA分化的SH-SY5Y细胞TH的表达降低了31%(P<0.01),100nM-48h组分化细胞TH的表达降低了89%(P<0.01)。与Con-24h组细胞相比,T处理使10nM-24h组RA/TPA分化的SH-SY5Y细胞DAT的表达升高了90%(P<0.01),100nM-24h组分化细胞DAT的表达升高了91%(P<0.01);与Con-48h组细胞相比,T处理后10nM-48h组RA/TPA分化的SH-SY5Y细胞DAT的表达升高了47%(P<0.05),100nM-48h组分化细胞DAT的表达升高了84%(P<0.01)。
4. RT-PCR结果显示,与Con-24h组细胞相比,T处理后10nM-24h组细胞TH mRNA的表达升高了41%(P<0.05),100nM-24h组细胞THmRNA的表达无显著变化;Con-48h、10nM-48h和100nM-48h三组细胞间TH mRNA的表达无显著差异。
结论:
1. RA/TPA可以诱导SH-SY5Y细胞向成熟神经元分化。
2.10nM和100nM的T处理分化的SH-SY5Y细胞24小时和48小时对细胞活力没有显著影响。
3.10nM T处理24小时可以显著增加分化的SH-SY5Y细胞的THmRNA和蛋白表达,而其他剂量和处理时间的T则降低TH的表达,表明T增加DA能神经元TH表达的作用是低剂量短时效性的。
4.10nM和100nM T处理24和48小时均使分化的SH-SY5Y细胞DAT表达升高,表明T增强了DA能神经元功能状态。
The motor behavior and the motor performance involving balance,coordination, and strength decline significantly in aged man and aged animals,which is the hallmark of aging. The nigrostriatal dopaminergic (NSDA)system, which is involved in motor control, also accordingly undergoes aprogressive decline during normal aging, such as a decrease in tyrosinehydroxylase (TH) and its mRNA, as well as in dopamine transporter (DAT)and its mRNA, which implicate the impairment of dopaminergic system inaged animals. The impaired NSDA system may contribute to the significantdecline in motor behavior and motor performance in aged animals.
The influence of anabolic androgenic steroids (AAS) on centraldopaminergic activity and behaviors of organisms has been reported in animalstudies. Supplement of testosterone increases anti-anxiety behavior andenhances cognitive performance in aged intact male mice. Some parameters ofthe open field activity in rats are improved by testosterone. Relatively highdoses of AAS increases dopaminergic metabolism in male rat brain. Theadministration of testosterone to castrated rats completely prevents thecastration-induced reduction of striatal TH activity.
Injections with glial cell line-derived neurotrophic factor can increaselocomotor activity of aged rats through enhancing TH activity in the substantianigra (SN) and striatum of aged rats. It implies exogenous interventions act onthe NSDA system and affect locomotor activity of aged rats. Aged rats havelower level of testosterone in serum. Long term testosterone replacement mayfavorably alter the decline in the process of sexual activity with aging and therestoration by testosterone replacement of dopaminergic activity in the medialpreoptic area may be involved in the maintenance of sexual function in aged rats. To date, it is not known whether exogenous testosterone intervention toaged male rats ameliorates the impaired motor behavior and motorperformance by altering NSDA system. Testosterone involved in theneuropathophysiology of Parkinson's disease. The resting tremor, fine motorcontrol and nonmotor symptom are significantly improved in a parkinsonianpatient with testosterone deficiency following testosterone treatment and theimprovement in motor symptoms is correlated with serum testosteronesupplement levels. We presume that androgen supplement might amelioratethe declined motor behavior and motor performance of aged rats by alteringNSDA system.
Therefore, in the present study, the motor-related behaviors of aged malerats after testosterone propionate (TP) treatment were observed by open fieldtest, tilting-plane test, horizontal-wire test as well as adhesive removal test andthe effect of chronic administration of TP on aged rats was investigated byanalysing the altered expression of TH and DAT in NSDA system. In order tospeculate the mechanism of ameliorate effects of androgen on NSDA system,the effect of T on the expression of TH and DAT in differentiated SH-SY5Ycell was tested. It is hoped that supplement of androgen could be used inadjutant therapy for age-dependent motor deficits.
Part1: The amelioratory effect of TP on motor-related behaviors in agedmale rats
Objective: To study the effects of chronic administration of TP onmotor-related behaviors in aged male rats.
Methods: The open field test, tilting-plane test, horizontal-wire test andadhesive removal test were used to analyse the effects of TP on motor-relatedbehaviors in aged male rats. Radioimmunoassay (RIA) was used to detecttestosterone concentration in serum after administration of TP
Results:
1. Open field test: The amount of immobile-sniffing events, walking,climbing,rearing,sniffing, vertical activity, horizontal activity, total path length, number of grooming events and the duration of grooming wasdecreased in24Mon rats by39%(P<0.01),52%(P<0.01),39%(P<0.01),69%(P<0.01),51%(P<0.01),50%(P<0.01),56%(P<0.01),55%(P<0.01),59%(P<0.01) and55%(P<0.01) respectively, and the latency of groomingwas increased by392%(P<0.01) compared to6Mon rats. After TP treatment,the amount of immobile-sniffing events, climbing,rearing,sniffing andvertical activity was significantly increased in24Mon-TP rats by27%(P<0.05)、37%(P<0.05)、97%(P<0.01)、44%(P<0.05) and52%(P<0.05)respectively compared to24Mon rats. The amount of climbing in24Mon-TPrats failed to differ significantly from that in6Mon rats.
2. Tilting-plane test: The angle of sliding off decreased by22%(P<0.01)and the number of sliding off at50°angle increased by550%(P<0.01) in24Mon rats compared to6Mon rats. After TP treatment, the angle of slidingoff was significantly increased (P<0.05) and the number of sliding off at50°angle was significantly decreased (P<0.01).
3. Horizontal-wire test: The duration time of hanging was shorter by62%(P<0.01) in24Mon rats compared to6Mon rats. Administration of TPimproved the duration time of hanging compared to24Mon rats (P<0.01).
4. Adhesive removal test: The latency to remove adhesive paper on leftnose and right nose increased by382%(P<0.01) and577%(P<0.01)respectively in24Mon rats compared to6Mon rats. The latency to removeadhesive paper on left forepaw and right forepaw increased by1410%(P<0.01) and1156%(P<0.01) in24Mon rats respectively. TP treatmentdecreased the latency to remove adhesive paper on the nose (P<0.05) andforepaw (P<0.01) of aged rat significantly.
5. Testosterone in serum was decreased by61%(P<0.05) in24Mon ratscompared to6Mon rats. Administration of TP increased the level of serumtestosterone in24Mon-TP rats significantly (P<0.01).
Conclusions:
1. The open field behavior was significantly lower in24Mon rats than in6Mon rats. Administration of TP ameliorated the open field behavior of aged male rats.
2. The balancing reactions, muscular strength performance and motorcoordination ability were significantly reduced in24Mon rats compared to6Mon rats, which were improved after chronic TP administration.
3. Administration of TP increased the level of serum testosterone in agedmale rats.
Part2: Administration of TP increased the expression of TH and DAT innigrostriatal dopaminergic neurons of aged male rats
Objective: To study the influence of chronic administration of TP on theexpression of TH and DAT in nigrostriatal dopaminergic neurons of aged rats.
Methods: Immunohistochemistry and immunoblotting was used to detectthe expression of TH and DAT in nigrostriatal dopaminergic neurons.
Results:
1. Immunocytochemistry: The expression of TH in24Mon rats wasdecreased by25%(P<0.01) in SN and28%(P<0.01) in CPu. Chronicadministration of TP increased the expression of TH in SN and CPu of agedrats by14%(P<0.01) and26%(P<0.01) respectively. The expression of DATwas decreased by22%(P<0.01) in SN and32%(P<0.01) in CPu respectivelyin24Mon rats compared to6Mon rats. Chronic administration of TP improvedthe expression of DAT in SN (P<0.01) and CPu (P<0.05). The expression ofDAT in SN of24Mon-TP rats restored to the level of6Mon rats.
2. Immunoblotting: The expression of TH was decreased by28%(P<0.01),36%(P<0.01) in SN and CPu in24Mon rats compared to6Mon ratsrespectively. Chronic treatment of TP increased the expression of TH by22%(P<0.01),68%(P<0.01) in SN and CPu respectively. The expression ofGlyco-DAT and Non-Glyco-DAT were decreased by54%(P<0.01) and26%(P<0.05) in SN respectively,71%(P<0.01) and39%(P<0.01) in CPurespectively. The expression of Non-Glyco-DAT in CPu and expression ofGlyco-DAT in SN and CPu of aged rats increased by35%(P<0.05),74% (P<0.01) and89%(P<0.01) respectively after chronic TP treatment. Theexpression of Non-Glyco-DAT in SN was not influenced by TP.
Conclusions:
1. The expression of TH and DAT in SN and CPu of aged rats wassignificantly reduced, which was improved after chronic administration of TP.
2. The expression of Glyco-DAT and Non-Glyco-DAT in SN and CPu ofaged rats was significantly decreased. After chronic TP treatment, theexpression of Non-Glyco-DAT in CPu and expression of Glyco-DAT in SNand CPu of aged rats improved significantly, but the expression ofNon-Glyco-DAT in SN was not influenced. It implies that TP may act on theglycosylation of DAT.
Part3: The chronic treatment of TP increased the expression of THmRNA and DAT mRNA in nigrostriatal dopaminergic neurons of agedmale rats
Objective: To study the influence of TP on the expression of TH andDAT in nigrostriatal dopaminergic neurons of aged rats at the transcriptionallevel.
Methods: Total RNA extraction and RT-PCR was used to detect theexpression of TH mRNA and DAT mRNA in SN.
Results: The expression of TH mRNA (P<0.01) and DAT mRNA(P<0.01) in SN of24Mon rats was significantly reduced compared to6Monrats. The expression of TH mRNA (P<0.01) and DAT mRNA (P<0.01) in24Mon-TP rats increased significantly and failed to differ significantly fromthat in6Mon rats.
Conclusions: Chronic treatment of TP restored the decreased expressionof TH mRNA and DAT mRNA in aged rats to the level of6Mon rats. Itsuggests TP could influence the expression of TH and DAT at transcriptionallevel.
Part4: Influence of T on the expression of TH and DAT in differentiatedSH-SY5Y cells
Objective: To study the influence of T on the dopaminergic activity indifferentiated SH-SY5Y cells.
Methods: SH-SY5Y cells treated with RA/TPA for6days.
Immunoblotting and RT-PCR was used to detect the expression of TH and
DAT in differentiated SH-SY5Y cells.
Results:
1. After treated with RA/TPA for6days, the shape of SH-SY5Y cellschanged obviously with long neuritic processes and the expresssion of NeuNwas elevated.
2. After treated with10nM or100nM T for24h or48h, the viability ofdifferentiated SH-SY5Y cells did not change by the trypan blue exclusionassay and MTT assay.
3. Immunoblotting: The expression of TH was increased by123%(P<0.01) in10nM-24h cells compared to Con-24h cells while decreased by58%(P<0.01) in100nM-24h cells. Compared to Con-48h cells, theexpression of TH was decreased by31%(P<0.01) and89%(P<0.01) in10nM-48h and100nM-48h cells respectively. The expression of DAT wasincreased by90%(P<0.01) and91%(P<0.01) in10nM-24h and100nM-24hcells respectively compared to Con-24h cells. Compared to Con-48h cells, theexpression of DAT was increased by47%(P<0.05) and84%(P<0.01) in10nM-48h and100nM-48h respectively.
4. RT-PCR:Compared to Con-24h cells, the expression of TH mRNAwas increased by41%(P<0.05) in10nM-24h cells, but the expression of THmRNA in100nM-24h cells didn’t show any difference with Con-24h cells.Group differences among Con-48h,10nM-48h and100nM-48h cells in theexpression of TH mRNA were not found.
Conclusions:
1. RA/TPA induced SH-SY5Y cell to develop phenotype of maturedopaminergic neuron.
2. Treatment with10nM or100nM T for24h or48h didn’t influence theviability of differentiated SH-SY5Y cells.
3. Treatment with10nM T for24h increased the expression of THmRNA and protein in differentiated SH-SY5Y cells while other dosages andduration of T decreased the expression of TH mRNA and protein. It impliesthat T only improves the experssion of TH in low dosage and short duration.
4. Treatment with10nM or100nM T for24h or48h increased theexpression of DAT significantly. It suggests T improve the activity ofdopaminergic neuron.
引文
1Kish SJ, Shannak K, Rajput A, et al. Aging produces a specific pattern ofstriatal dopamine loss: implications for the etiology of idiopathicParkinson's disease [J]. J Neurochem,1992,58(2):642-648
2Meng SZ, Ozawa Y, Itoh M, et al. Developmental and age-related changesof dopamine transporter, and dopamine D1and D2receptors in humanbasal ganglia [J]. Brain Res,1999,843(1-2):136-144
3Bennett DA, Beckett LA, Murray AM, et al. Prevalence of parkinsoniansigns and associated mortality in a community population of older people[J]. N Engl J Med,1996,334(2):71-76
4Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson’sdisease [J]. Adv Neurol,1987,45:19-34
5Stanford JA, Hebert ME, Gerhardt GA. Biochemical and anatomicalchanges in basal ganglia of aging animals. In: Hof PR, Mobbs CV, editors.Functional neurobiology of aging. New York: Academic Press;2001,727-736
6Cruz-Muros I, Afonso-Oramas D, Abreu P, et al. Aging effects on thedopamine transporter expression and compensatory mechanisms [J].Neurobiol Aging,2009,30(6):973-986
7Frye CA., Edinger K, Sumida K. Androgen administration to aged malemice increases anti-anxiety behavior and enhances cognitive performance[J]. Neuropsychopharmacology,2008,33(5):1049-1061
8Zhang G, Shi G, Tan H, et al. Intranasal administration of testosteroneincreased immobile-sniffing, exploratory behavior, motor behavior andgrooming behavior in rats [J]. Horm Behav,2011,59(4):477-483
9Abreu P, Hernandez G, Calzadilla CH, et al. Reproductive hormonescontrol striatal tyrosine hydroxylase activity in the male rat [J]. NeurosciLett,1988,95(1-3):213-217
10Lapchak PA, Miller PJ, Jiao S. Glial cell line-derived neurotrophic factorinduces the dopaminergic and cholinergic phenotype and increaseslocomotor activity in aged Fischer344rats [J]. Neuroscience,1997,77(3):745-752
11Putnam SK, Du J, Sato S, et al. Testosterone restoration of copulatorybehavior correlates with medial preoptic dopamine release in castratedmale rats [J]. Horm Behav,2001,39(3):216-224
12Ghanadian R, Lewis JG, Chisholm GD. Serum testosterone anddihydrotestosterone changes with age in rat [J]. Steroids,1975,25(6):753-762
13Okun MS, Walter BL, McDonald WM, et al. Beneficial Effects ofTestosterone Replacement for the Nonmotor Symptoms of ParkinsonDisease [J]. Arch Neurol,2002,59(11):1750-1753
14Ready RE, Friedman J, Grace J, et al. Testosterone deficiency and apathyin Parkinson's disease: a pilot study [J]. J Neurol Neurosurg Psychiatry,2004,75(9):1323-1326
15Mitchell E, Thomas D, Burnet R. Testosterone improves motor function inParkinson’s disease [J]. J Clin Neurosci,2006,13(1):133-136
16J nicke B, Schulze G, Coper H. Motor performance achievements in rats ofdifferent ages [J]. Exp Gerontol,1983,18(5):393-407
17Emerich DF, McDermott P, Krueger P, et al. Locomotion of aged rats:relationship to neurochemical but not morphological changes innigrostriatal dopaminergic neurons [J]. Brain Res Bull,1993,32(5):477-486
18Sanchez HL, Silva LB, Portiansky EL, et al. Dopaminergic mesencephalicsystems and behavioral performance in very old rats [J]. Neuroscience,2008,154(4):1598-1606
19Emborg ME, Ma SY, Mufson EJ, et al. Age-related declines in nigralneuronal function correlate with motor impairments in rhesus monkeys [J].J Comp Neurol,1998,401(2):253-265
20Edinger KL, Frye CA. Testosterone's anti-anxiety and analgesic effectsmay be due in part to actions of its5alpha-reduced metabolites in thehippocampus [J]. Psychoneuroendocrinology,2005,30(5):418-430
21Adler A, Vescovo P, Robinson JK, et al. Gonadectomy in adult lifeincreases tyrosine hydroxylase immunoreactivity in the prefrontal cortexand decreases open field activity in male rats [J]. Neuroscience,1999,89(3):939-954
22康云霄,李双成,高建伟,等。丙酸睾酮早期处理对大鼠行为及脑内多巴胺转运体的影响[J]。解剖学杂志,2008,31(5):655-657
23Casarrubea M, Sorbera F, Crescimanno G. Multivariate analysis of themodifications induced by an environmental acoustic cue on rat exploratorybehavior [J]. Physiol Behav,2008,93(4-5):687-996
24Casarrubea M, Sorbera F, Crescimanno G. Structure of rat behavior inhole-board: I) multivariate analysis of response to anxiety [J]. PhysiolBehav,2009,96(1):174-179
25Casarrubea M, Sorbera F, Crescimanno G. Structure of rat behavior inhole-board: II) multivariate analysis of modifications induced by diazepam[J]. Physiol Behav,2009,96(4-5):683-692
26Meyerson BJ, H glund AU. Exploratory and socio-sexual behaviour in themale laboratory rat: a methodological approach for the investigation ofdrug action [J]. Acta Pharmacol Toxicol (Copenh),1981,48(2):168-180
27Prut L, Belzung C. The open field as a paradigm to measure the effects ofdrugs on anxiety-like behaviors: a review [J]. Eur J Pharmacol,2003,463(1-3):3-33
28Ericson E, Samuelsson J, Ahlenius S. Photocell measurements of rat motoractivity. A contribution to sensitivity and variation in behavioralobservations [J]. J Pharmacol Methods,1991,25(2):111-122
29Hillegaart V, Wadenberg ML, Ahlenius S. Effects of8-OH-DPAT on motoractivity in the rat [J]. Pharmacol Biochem Behav,1989,32(3):797-800
30Wultz B, Sagvolden T, Moser EI, et al. The spontaneously hypertensive ratas an animal model of attention-deficit hyperactivity disorder: effects ofmethylphenidate on exploratory behavior [J]. Behav Neural Biol,1990,53(1):88-102
31Li JS, Huang YC. Early androgen treatment influences the pattern andamount of locomotion activity differently and sexually differentially in ananimal model of ADHD [J]. Behav Brain Res,2006,175(1):176-182
32Kalueff AV, Tuohimaa P. Grooming analysis algorithm forneurobehavioural stress research [J]. Brain Res Brain Res Protoc,2004,13(3):151-158
33Kalueff AV, Tuohimaa P. The grooming analysis algorithm discriminatesbetween different levels of anxiety in rats: potential utility forneurobehavioural stress research [J]. J Neurosci Methods,2005,143(2):169-177
34Kalueff AV, Aldridge JW, LaPorte JL, et al. Analyzing groomingmicrostructure in neurobehavioral experiments [J]. Nat Protoc,2007,2(10):2538-2544
35Schallert T, Upchurch M, Lobaugh N, et al. Tactile extinction:distinguishing between sensorimotor and motor asymmetries in rats withunilateral nigrostriatal damage [J]. Pharmacol. Biochem Behav,1982,16(3):455-462
36Chen L, Cagniard B, Mathews T, et al. Age-dependent motor deficits anddopaminergic dysfunction in DJ-1null mice [J]. J Biol Chem,2005,280(22):21418-21426
37Sato Y, Shibuya A, Adachi H, et al. Restoration of sexual behavior anddopaminergic neurotransmission by long term exogenous testosteronereplacement in aged male rats [J]. J Urol,1998,160(4):1572-1575
38Janowsky JS. The role of androgens in cognition and brain aging in men [J].Neuroscience,2006,138(3):1015-1020
39Zahm DS, Trimble M. The dopaminergic projection system, basalforebrain macrosystems, and conditioned stimuli [J]. CNS Spectr,2008,13(1):32-40
40Albin RL, Young AB, Penney JB. The functional anatomy of basal gangliadisorders [J]. Trends Neurosci,1989,12(10):366-375
41Albin RL. Neurobiology of basal ganglia and Tourette syndrome: striataland dopamine function [J]. Adv Neurol,2006,99:99-106
42Berridge KC, Aldridge JW, Houchard KR, et al. Sequentialsuper-stereotypy of an instinctive fixed action pattern inhyper-dopaminergic mutant mice: a model of obsessive compulsivedisorder and Tourette's [J]. BMC Biol,2005,14:3-4
1Kish SJ, Shannak K, Rajput A, et al. Aging produces a specific pattern ofstriatal dopamine loss: implications for the etiology of idiopathicParkinson's disease [J]. J Neurochem,1992,58(2):642-648
2Meng SZ, Ozawa Y, Itoh M, et al. Developmental and age-related changesof dopamine transporter, and dopamine D1and D2receptors in humanbasal ganglia [J]. Brain Res,1999,843(1-2):136-144
3De La Cruz CP, Revilla E, Venero JL, et al. Oxidative inactivation oftyrosine hydroxylase in substantia nigra of aged rat [J]. Free Radic BiolMed,1996,20(1):53-61
4Emborg ME, Ma SY, Mufson EJ, et al. Age-related declines in nigralneuronal function correlate with motor impairments in rhesus monkeys [J].J Comp Neurol,1998,401(2):253-265
5McCormack AL, Di Monte DA, Delfani K, et al. Aging of the nigrostriatalsystem in the squirrel monkey [J]. J Comp Neurol,2004.471(4):387-395
6Sanchez HL, Silva LB, Portiansky EL, et al. Dopaminergic mesencephalicsystems and behavioral performance in very old rats [J]. Neuroscience,2008,154(4):1598-1606
7Tümer N, LaRochelle JS, Yürekli M.. Exercise training reverses theage-related decline in tyrosine hydroxylase expression in rat hypothalamus[J]. J Gerontol A Biol Sci Med Sci,1997,52(5): B255-B259
8Cruz-Muros I, Afonso-Oramas D, Abreu P, et al. Aging effects on thedopamine transporter expression and compensatory mechanisms [J].Neurobiol Aging,2009,30(6):973-986
9Emerich DF, McDermott P, Krueger P, et al. Locomotion of aged rats:relationship to neurochemical but not morphological changes innigrostriatal dopaminergic neurons [J]. Brain Res Bull,1993,32(5):477-486
10Irwin I, DeLanney LE, McNeill T. et al. Aging and the nigrostriataldopamine system: a non-human primate study [J]. Neurodegeneration,1994,3(4):251-265
11J nicke B, Schulze G, Coper H. Motor performance achievements in ratsof different ages [J]. Exp Gerontol,1983,18(5):393-407
12Vermes I, Várszegi M, Tóth EK, et al. Action of androgenic steroids onbrain neurotransmitters in rats [J]. Neuroendocrinology,1979,28(6):386-393
13Kindlundh AM, Bergstrom M, Monazzam A, et al. Dopaminergic effectsafter chronic treatment with nandrolone visualized in rat brain by positronemission tomography [J]. Prog Neuropsychopharmacol Biol Psychiatry,2002,26(7-8):1303-1308
14Kindlundh AM, Rahman S, Lindblom J, et al. Increased dopaminetransporter density in the male rat brain following chronic nandrolonedecanoate administration [J]. Neurosci Lett,2004,356(2):131-134
15Thiblin I, Finn A, Ross SB, et al. Increased dopaminergic and5-hydroxytryptaminergic activities in male rat brain following long-termtreatment with anabolic androgenic steroids [J]. Br J Pharmacol,1999,126(6):1301-1306
16Abreu P, Hernandez G, Calzadilla CH, et al. Reproductive hormonescontrol striatal tyrosine hydroxylase activity in the male rat [J]. NeurosciLett,1988,95(1-3):213-217
17Lapchak PA, Miller PJ, Jiao S. Glial cell line-derived neurotrophic factorinduces the dopaminergic and cholinergic phenotype and increaseslocomotor activity in aged Fischer344rats [J]. Neuroscience,1997,77(3):745-752
18Houk JC, Davis JL, Beiser DG, et al. Models of Information Processing inthe Basal Ganglia. Cambridge, Mass: MIT Press;1995
19Uhl GR. Dopamine transporter: basic science and human variation of akey molecule for dopaminergic function, locomotion, and parkinsonism[J]. Mov Disord.2003.18(Suppl.7): S71-S80
20de Souza Silva MA, Mattern C, Topic B, et al. Dopaminergic andserotonergic activity in neostriatum and nucleus accumbens enhanced byintranasal administration of testosterone [J]. Eur Neuropsychopharmacol,2009,19(1):53-63
21Mitchell JB, Stewart J. Effects of castration, steroid replacement, andsexual experience on mesolimbic dopamine and sexual behaviors in themale rat [J]. Brain Res,1989,491(1):116-127
22Martinez-Sanchis S, Aragon CM, Salvador A, Cocaine-induced locomotoractivity is enhanced by exogenous testosterone [J]. Physiol Behav,2002,76(4-5):605-609
23Clark AS, Barber DM. Anabolic-androgenic steroids and aggression incastrated male rats [J]. Physiol Behav,1994,56(5):1107-1113
24Kritzer MF. Selective colocalization of immunoreactivity for intracellulargonadal hormone receptors and tyrosine hydroxylase in the ventraltegmental area, substantia nigra, and retrorubral fields in the rat [J]. JComp Neurol,1997,379(2):247-260
25Simerly RB, Chang C, Muramatsu M, et al. Distribution of androgen andestrogen receptor mRNA-containing cells in the rat brain: an in situhybridization study [J]. J Comp Neurol,1990,294(1):76-95
26Shughrue PJ, Merchenthaler I. Distribution of estrogen receptor betaimmunoreactivity in the rat central nervous system [J]. J Comp Neurol,2001,436(1):64-81
27Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution ofestrogen receptor-alpha and-beta mRNA in the rat central nervous system[J]. J Comp Neurol,1997,388(4):507-525
28Dluzen DE, Ramirez VD. Effects of orchidectomy on nigro-striataldopaminergic function: behavioral and physiological evidence [J]. JNeuroendocrinol,1989,1(4):285-290
29Hernandez L, Gonzalez L, Murzi E, et al. Testosterone modulatesmesolimbic dopaminergic activity inmale rats [J]. Neurosci Lett,1994,171(1-2):172-174
30Long SF, Dennis LA, Russell RK, et al. Testosterone implantation reducesthe motor effects of cocaine [J]. Behav Pharmacol,1994,5(1):103-106
31Ciliax BJ, Heilman C, Demchyshyn LL, et al. The dopamine transporter:immunochemical characterization and localization in brain [J]. J Neurosci,1995,15(3Pt1):1714-1723
32Simonyi A, Miller LA, Sun GY. Region-specific decline in the expressionof metabotropic glutamate receptor7mRNA in rat brain during aging [J].Brain Res Mol Brain Res,2000,82(1-2):101-106
33S r s P, Bose A, Sokoloff LG, et al. Age-related changes in the functionalneuroanatomy of overt speech production [J]. Neurobiol Aging,2009,32(8):1505-1513
1Kish SJ, Shannak K, Rajput A, et al. Aging produces a specific pattern ofstriatal dopamine loss: implications for the etiology of idiopathicParkinson's disease [J]. J Neurochem,1992,58(2):642-648
2Yoshimoto K, Kato B, Ueda S, et al. Dopamine and serotonin uptakeinhibitors on the release of dopamine and serotonin in the nucleusaccumbens of young and aged rats [J]. Mech Ageing Dev,2001,122(15):1707-1721
3De La Cruz, CP, Revilla E, Venero JL, et al. Oxidative inactivation oftyrosine hydroxylase in substantia nigra of aged rat [J]. Free Radic Bio.Med,1996,20(1):53-61
4王磊,康云霄,石葛明.老年人脑内多巴胺转运体的表达[J].中国老年学杂志,2008,28(16):1607-1608
5康云霄,王磊,王智涛,等.老年大鼠脑内多巴胺转运体的表达[J].中国老年学杂志,2008,28(6):527-529
6Emborg ME, Ma SY, Mufson EJ, et al. Age-related declines in nigralneuronal function correlate with motor impairments in rhesus monkeys [J].J Comp Neurol,1998,401(2):253-265
7Vermes I, Várszegi M, Tóth EK, et al. Action of androgenic steroids onbrain neurotransmitters in rats [J]. Neuroendocrinology,1979,28(6):386-393
8Kindlundh AM, Bergstrom M, Monazzam A., et al. Dopaminergic effectsafter chronic treatment with nandrolone visualized in rat brain by positronemission tomography [J]. Prog Neuropsychopharmacol Biol Psychiatry,2002,26(7-8):1303-1308
9Kindlundh AM, Rahman S, Lindblom J, et al. Increased dopaminetransporter density in the male rat brain following chronic nandrolonedecanoate administration [J]. Neurosci Lett,2004,356(2):131-134
10Thiblin I, Finn A, Ros, SB, et al. Increased dopaminergic and5-hydroxytryptaminergiactivities in male rat brain following long-termtreatment with anabolic androgenic steroids [J]. Br J Pharmaco,1999,126(6):1301-1306
11Birgnera C, Kindlundh-H gbergb AM, Alsi b J, et al. The anabolicandrogenic steroid nandrolone decanoate affects mRNA expression ofdopaminergic but not serotonergic receptors [J]. Brain Res,2008,1240:221-228
12Bowyer JF, Frame LT, Clausing P, et al. Long-term effects ofamphetamine neurotoxicity on tyrosine hydroxylase mRNA and protein inaged rats [J]. J Pharmacol Exp Ther,1998,286(2):1074-1085
13Cruz-Muros I, Afonso-Oramas D, Abreu P, et al. Aging effects on thedopamine transporter expression and compensatory mechanisms [J].Neurobiol Aging,2009,30(6):973-986
14Iwasaki-Ishizuka Y, Yamato H, Nii-Kono T, et al. Downregulation ofparathyroid hormone receptor gene expression and osteoblasticdysfunction associated with skeletal resistance to parathyroid hormone in arat model of renal failure with low turnover bone [J]. Nephrol DialTransplant,2005,20(9):1904-1911
15Bannon MJ, Poosch MS, Xia Y. Goebel DJ, Cassin B, Kapatos G.Dopamine transporter mRNA content in human substantia nigra decreasesprecipitously with age [J]. Proc Natl Acad Sci USA,1992,89:7095-7099
16Bannon MJ, Whitty CJ. Age-related and regional differences in dopaminetransporter mRNA expression in human midbrain [J]. Neurology,1997,48(4):969-977
17Himi T, Cao M, Mori N. Reduced expression of the molecular markers ofdopaminergic neuronal atrophy in the aging rat brain. J Gerontol [J]. ABiol Sci Med Sci,1995,50(4): B193-B200
18Nagatsu T, Levitt M, S. Udenfriend, Tyrosine hydroxylase. The initial stepin norepinephrine biosynthesis [J]. J Biol Chem,1964,239:2910-2917
19Baruchin A, Weisberg EP, Miner LL, et al. Effects of cold exposure on ratadrenal tyrosine hydroxylase: an analysis of RNA, protein, enzyme activity,and cofactor levels [J]. J Neurochem,1990,54(5):1769-1775
20Fossom LH, Sterling CR, Tank AW. Regulation of tyrosine hydroxylasegene transcription rate and tyrosine hydroxylase mRNA stability by cyclicAMP and glucocorticoid [J]. Mol Pharmacol,1992,42(5):898-908
21Kumer SC, Vrana KE, Intricate regulation of tyrosine hydroxylase activityand gene expression [J]. J Neurochem,1996,67(2):443-462
22Doering C, Leyra PT. Methyltrienolone (R1881) is not aromatized byplacental microsomes or rat hypothalamic homogenates [J]. SteroidBiochem,1984,20(5):1157-1162
23Thanky NR, Son JH, Herbison AE. Sex differences in the regulation oftyrosine hydroxylase gene transcription by estrogen in the locus coeruleusof TH9-LacZ transgenic mice [J]. Brain Res Mol Brain Res,2002,104(2):220-226
24Jeong H, Kim MS, Kwon J, et al. Regulation of the transcriptional activityof the tyrosine hydroxylase gene by androgen receptor [J]. Neurosci Lett,2006,396(1):57-61
25Maharjan S, Serova L, Sabban EL. Transcriptional regulation of tyrosinehydroxylase by estrogen: opposite effects with estrogen receptors alphaand beta and interactions with cyclic AMP [J]. J Neurochem,2005,93(6):1502-1514
26Kritzer MF. Selective colocalization of immunoreactivity for intracellulargonadal hormone receptors and tyrosine hydroxylase in the ventraltegmental area, substantia nigra, and retrorubral fields in the rat [J]. JComp Neurol,1997,379(2):247-260
27Simerly RB, Chang C, Muramatsu M, et al. Distribution of androgen andestrogen receptor mRNA-containing cells in the rat brain: an in situhybridization study [J]. J Comp Neurol,1990,294(1):76-95
28Shughrue PJ, Merchenthaler I. Distribution of estrogen receptor betaimmunoreactivity in the rat central nervous system [J]. J Comp Neurol,2001,436(1):64-81
29Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution ofestrogen receptor-alpha and-beta mRNA in the rat central nervous system[J]. J Comp Neurol,1997,388(4):507-525
30Li LB, Chen N, Ramamoorthy S, et al. The role of N-glycosylation infunction and surface trafficking of the human dopamine transporter [J]. JBiol Chem,2004,279(20):21012-21020
31Vaughan RA, Huff RA, Uhl GR, et al. Protein kinase C-mediatedphosphorylation and functional regulation of dopamine transporters instriatal synaptosomes [J]. J Biol Chem,1997,272(24):15541-15546
32Ferrini RL, Barrett-Connor E. Sex hormones and age: a cross-sectionalstudy of testosterone and estradiol and their bioavailable fractions incommunity-dwelling men [J]. Am J Epidemiol,1998,147(8):750-754
33Verghese J, Ambrose AF, Lipton RB, et al. Neurological gait abnormalitiesand risk of falls in older adults [J]. J Neurol,2010,257(3):392-398
1Biedler JL, Helson L, Spengler BA. Morphology and growth,tumorigenicity and cytogenetics of human neuroblastoma cells incontinuous culture [J]. Cancer Res,1973,33(11):2643-2652
2Joshi S, Guleria R, Pan J, et al. Retinoic acid receptors andtissue-transglutaminase mediate short-term effect of retinoic acid onmigration and invasion of neuroblastoma SH-SY5Y cells [J]. Oncogene,2006,25(2):240-247
3Ciccarone V, Spengler BA, Meyers MB, et al. Phenotypic diversificationin human neuroblastoma cells: expression of distinct neural crest lineages[J]. Cancer Res,1989,49(1):219-225
4Singh J, Kaur G. Transcriptional regulation of polysialylated neural celladhesion molecule expression by NMDA receptor activation in retinoicacid-differentiated SH-SY5Y neuroblastoma cultures [J]. Brain Res,2007,1154:8-21
5P hlman S, Odelstad L, Larsson E, et al. Phenotypic changes of humanneuroblastoma cells in culture induced by12-O-tetradecanoyl-phorbol-13-acetate [J]. Int J Cancer,1981,28(5):583-589
6Cernaianu G, Brandmaier P, Scholz G, et al. All-trans retinoic acid arrestsneuroblastoma cells in a dormant state. Subsequent nerve growthfactor/brain derived neurotrophic factor treatment adds modest benefit [J].J Pediatr Surg,2008,43(7):1284-1294
7Takahashi T, Deng Y, Maruyama W, et al. Uptake of aneurotoxin-candidate,(R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells bydopamine transport system [J]. J Neural Transm Gen Sect,1994,98(2):107-118
8Presgraves SP, Ahmed T, Borwege S, et al. Terminally differentiatedSH-SY5Y cells provide a model system for studying neuroprotectiveeffects of dopamine agonists [J]. Neurotox Res,2004,5(8):579-598
9Yerramilli-Rao P, Garofalo O, Whatley S, et al. Androgen-controlledspecific gene expression in neuroblastoma cells [J]. J Neurol Sci,1995,129:(Suppl)131-135
10Nagai A, Suzuki Y, Baek SY, et al. Generation and Characterization ofHuman Hybrid Neurons Produced between Embryonic CNS Neurons andNeuroblastoma Cells [J]. Neurobiol Dis,2002,11(1):184-198
11Pan T, Xie W, Jankovic J, et al. Biological effects of pramipexole ondopaminergic neuron-associated genes: relevance to neuroprotection [J].Neurosci Lett,2005,377(2):106-109
12Cheung YT, Lau WK, Yu MS, et al. Effects of all-trans-retinoic acid onhuman SH-SY5Y neuroblastoma as in vitro model in neurotoxicityresearch [J]. Neurotoxicology,2009,30(1):127-135
13XIE HR, HU LS, LI GY. SH-SY5Y human neuroblastoma cell line: invitro cell model of dopaminergic neurons in Parkinson’s disease [J]. ChinMed J,2010,123(8):1086-1092
14Jalava A, Heikkil J, Lintunen M, et al. Staurosporine induces a neuronalphenotype in SH-SY5Y human neuroblastoma cells that resembles thatinduced by the phorbol ester12-O-tetradecanoyl phorbol-13acetate (TPA)[J]. FEBS Lett,1992,300(2):114-118
15Presgraves SP, Ahmed T, Borwege S, et al. Terminally differentiatedSH-SY5Y cells provide a model system for studying neuroprotectiveeffects of dopamine agonists [J]. Neurotox Res,2004,5(8):579-598
16Estrada1M, Varshney A, Ehrlich BE. Elevated Testosterone InducesApoptosis in Neuronal Cells [J]. J Biol Chem,2006,281(35):25492-25501
17Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigraregional selectively [J]. Brain,1991,114(5),2283-2301
18Youdim MB. Iron in the brain: implications for Parkinson’s andAlzheimer’s diseases [J]. Mt Sinai J Med,1988,55(2):97-101
19Naoi M, Maruyama W. Cell death of dopamine neurons in aging andParkinson’s disease [J]. Mech Ageing Dev,1999,111(2-3):175-188
20Miyazaki I, Asanuma M. Dopaminergic neuron-specific oxidative stresscaused by dopamine itself [J]. Acta Med Okayama,2008,62(3):141-150
21Rommerts FFG. Testosterone:an overview of biosynthesis, transport,metabolism and action. In Nieschlag E and Berber HM.(eds.)Testosterone Action. Deficiency sub situation. Springer-verlag.1990,1-22
22Shughrue PJ, Merchenthaler I. Distribution of estrogen receptor betaimmunoreactivity in the rat central nervous system [J]. J Comp Neurol,2001,436(1):64-81
1Smidt MP, Smits SM, Burbach JP. Molecular mechanisms underlyingmidbrain dopamine neuron development and function [J]. Eur J Pharmacol,2003,480(1-3):75-88
2Schultz W. Behavioral dopamine signals [J]. Trends Neurosci,2007,30(5):203-210
3Bjorklund A, Dunnett SB. Fifty years of dopamine research [J]. TrendsNeurosci,2007,30(5):185-187
4Wise RA. Dopamine, learning and motivation [J]. Nat Rev Neurosci,2004,5(6):483-494
5Roy VS, Michael WV. Desire, Disease, and the Origins of theDopaminergic System [J]. Schizophrenia Bulletin,2008,34(2):212-219
6Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes[J]. Sports Med,2004,34(8):513-554
7Schwerin MJ, Corcoran KJ, Fisher L, et al. Social physique anxiety, bodyesteem, and social anxiety in bodybuilders and self-reported anabolicsteroid users [J]. Addictive Behav,1996,21(1):1-8
8Bahrke MS, Yesalis CE, Kopstein AN, et al. Risk factors associated withanabolic–androgenic steroid use among adolescents [J]. Sports Med,2000,
29(6):397-405
9Burnett KF, Kleiman ME. Psychological characteristics of adolescentsteroid users [J]. Adolescence,1994,29(113):81-89
10Perry PJ, Kutscher EC, Lund BC, et al. Measures of aggression and moodchanges in male weightlifters with and without androgenic anabolicsteroid use [J]. J Forensic Sci,2003,48(3):646-651
11Birgnera C, Kindlundh-H gbergb AM, Alsi b J, et al. The anabolicandrogenic steroid nandrolone decanoate affects mRNA expression ofdopaminergic but not serotonergic receptors [J]. Brain Res,2008,1240:221-228
12Kurling S, Kankaanp A, Ellermaa S, et al. The effect of sub-chronicnandrolone decanoate treatment on dopaminergic and serotonergicneuronal systems in the brains of rats [J]. Brain Research,2005,1044(1):67-75
13Carlsson A, Falck B, Hillarp NA. Cellular localization of brainmonoamines [J]. Acta Physiol Scand Suppl,1962,56(196):1-28
14Dahlstrom A, Fuxe K. Evidence for the existence ofmonoamine-containing neurons in the central nervous system. I.Demonstration of monoamines in the cell bodies of brain stem neurons [J].Acta Physiol Scand Suppl,1964,232:1-55
15Carlsson A. A paradigm shift in brain research [J]. Science,2001,294(5544):1021–1024
16Deutch AY, Roth RH. Pharmacology and biochemistry of synaptictransmission: Classic transmitters. From Molecules to Network. Byrne JH,Roberts JL, editors. New York: Elsevier Academic Press,2004, pp.245-278
17Th ny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis,regeneration and functions [J]. Biochem J,2000,347(Pt1):1-16
18Hokfelt T, Johansson O, Fuxe K, et al. Immunohistochemical studies onthe localization and distribution of monoamine neuron systems in the ratbrain. I. Tyrosine hydroxylase in the mes-and diencephalons [J]. Med Biol,1976,54(6):427-453
19Nestler EJ, Hyman SE, Malenka RC. Molecular Neuropharmacology. AFoundation for Clinical Neuroscience. McGraw‐Hill,2001, New York:pp.115-137
20Walter DS, Flockhart IR, Haynes MJ, et al. Effects of idazoxan oncatecholamine systems in rat brain [J]. Biochem Pharmacol,1984,33(16):2553-2557
21Snyder AM, Keller RW, Zigmond MJ. Dopamin efflux from striatal slicesafter intracerebral6‐hydroxydopamine: Evidence for compensatoryhyperactivity of residual terminals [J]. J Pharm Exp Ther,1990,253(2):867-876
22Vizi ES, Harsing LG Jr, Gaal J, et al. CH‐38083, a selective, potentantagonist of alpha‐2adrenoceptors [J]. J Pharmacol Exp Ther,1986,238(2):701-706
23Zhu MY, Juorio AV. Aromatic L-amino acid decarboxylase: biologicalcharacterization and functional role [J]. Gen Pharmacol,1995,26(4):681-696
24Hadjiconstantinou M, Neff NH. Enhancing aromatic L-aminoacid decarboxylase activity: implications for L-DOPA treatment inParkinson's disease [J]. CNS Neurosci Ther,2008,14(4):340-351
25Hammond C. Neurotransmitter release. Cellular and MolecularNeurobiology. Hammond C,1996, New York: Academic Press, pp.188-214
26Justice JB Jr, Nicolaysen LC, Michael AC. Modeling the dopaminergicnerve terminal [J]. J Neurosci Methods,1988,22(3):239-252
27Bergquist F, Nissbrandt H. Dopamine release in substantia nigra: Releasemechanisms and physiological function in motor control. DendriticNeurotransmitter Release. Ludwig M,2005, New York: Springer, pp.85-99
28Weihe E, Eiden LE. Chemical neuroanatomy of the vesicular aminetransporters [J]. FASEB J,2000,14(15):2435-2449
29Gether U, Andersen PH, Larsson OM, et al. Neurotransmitter transporters:Molecular function of important drug targets [J]. Trends Pharmacol Sci,2006,27(7):375-383
30Erickson JD, Eiden LE, Hoffman BJ. Expression cloning of areserpine-sensitive vesicular monoamine transporter [J]. Proc Natl AcadSci USA,1992,89(22):10993-10997
31Henry JP, Botton D, Sagne C, et al. Biochemistry and molecular biologyof the vesicular monoamine transporter from chromaffin granules [J]. JExp Biol,1994,196:251-262
32Krejci E, Gasnier B, Botton D, et al. Expression and regulation of thebovine vesicular monoamine transporter gene [J]. FEBS Lett,1993,335(1):27-32
33Jassen AK, Brown JM, Panas HN, et al. Variants of the primate vesicularmonoamine transporter-2[J]. Brain Res Mol Brain Res,2005,139(2):251-257
34Cruz-Muros I, Afonso-Oramas D, Abreu P, et al. Deglycosylation andsubcellular redistribution of VMAT2in the mesostriatal system duringnormal aging [J]. Neurobiology of Aging,2008,29(11):1702-1711
35Rice ME, Patel JC, Cragg SJ. Dopamine release in the basal ganglia [J].Neuroscience,2011,198:112-137
36Grace AA. Phasic versus tonic dopamine release and the modulation ofdopamine system responsivity: A hypothesis for the etiology ofschizophrenia [J]. Neuroscience,1991,41(1):1-24
37Vizi ES. Role of high‐affinity receptors and membrane transporters innonsynaptic communication and drug action in the CNS [J]. PharmacolRev,2000,52(1):63-89
38Leviel V. The reverse transport of DA, what physiological significance [J]?Neurochem Int,2001,38(2):83-106
39Leviel V. Dopamine release mediated by the dopamine transporter, factsand consequences [J]. J Neurochem,2011,118(4):475-89
40Gnegy ME. The effect of phosphorylation on amphetamine‐mediatedoutward transport [J]. Eur J Pharmacol,2003,479(1-3):83-91
41Lonart G, Zigmond MJ. High glutamate concentrations evoke Ca(++)‐independent dopamine release from striatal slices: A possible role ofreverse dopamine transport [J]. J Pharmacol Exp Ther,1991,256(3):1132-1138
42Wonnacott S, Gothert M, Chahl LA, et al. Modulation of neurotransmitterrelease by some therapeutic and socially used drugs. Neurotransmitterrelease and its Modulation. Powis DA, Bunn SJ, editors, CambridgeUniversity Press,1995, pp.293-328
43Harsing LG Jr, Sershen H, Vizi SE, et al. N‐type calcium channels areinvolved in the dopamine releasing effect of nicotine [J]. Neurochem Res,1992,17(7):729-734
44van den Pol AN. Excitatory neuromodulator reduces dopamine release,enhancing prolactin secretion [J]. Neuron,2010,65(2):147-149
45Giros B, Caron MG. Molecular characterization of the dopaminetransporter [J]. Trends Pharmacol Sci,1993,14(2):43-49
46Horn AS. Dopamine uptake: a review of progress in the last decade [J].Prog Neurobiol,1990,34(5):387-400
47Uhl GR. Dopamine transporter: basic science and human variation of akey molecule for dopaminergic function, locomotion, and parkinsonism[J]. Mov Disord,2003,18(Suppl.7): S71-S80
48Shimada S, Kitayama S, Lin CL, et al. Cloning and expression of acocaine-sensitive dopamine transporter complementary DNA [J]. Science,1991,254(5031):576-578
49Vaughan RA. Phosphorylation and regulation of psychostimulant-sensitiveneurotransmitter transporters [J]. J Pharmacol Exp Ther,2004,310(1):1-7
50Gresch PJ, Sved AF, Zigmond MJ, et al. Local influence of endogenousnorepinephrine on extracellular dopamine in rat medial prefrontal cortex[J]. J Neurochem,1995,65(1):111-116
51Li LB, Chen N, Ramamoorthy S, et al. The role of N-glycosylation infunction and surface trafficking of the human dopamine transporter [J]. JBiol Chem,2004,279(20):21012-21020
52Cruz-Muros I, Afonso-Oramas D, Abreu P, et al. Aging effects on thedopamine transporter expression and compensatory mechanisms [J].Neurobiology of Aging,2009,30(6):973-986
53Han W, Rhee JS, Maximov A, et al. N-Glycosylation is essential forvesicular targeting of synaptotagmin1[J]. Neuron,2004,41(1):85-99
54Vaughan RA, Huff RA, Uhl GR, et al. Protein kinase C-mediatedphosphorylation and functional regulation of dopamine transporters instriatal synaptosomes [J]. J Biol Chem,1997,272(24):15541-15546
55Torres GE, Carneiro A, Seamans K, et al. Oligomerization and traffickingof the human dopamine transporter. Mutational analysis identifies criticaldomains important for the functional expression of the transporter [J]. JBiol Chem,2003,278(4):2731-2739
56Norregaard L, Gether U. The monoamine neurotransmitter transporters:Structure, conformational changes and molecular gating [J]. Curr OpinDrug Discov Devel,2001,4(5):591-601
57Gainetdinov RR, Sotnikova TD, Caron MG. Monoamine transporterpharmacology and mutant mice [J]. Trends Pharmacol Sci,2002,23(8):367-373
58Blum D, Torch S, Lambeng N, et al. Molecular pathways involved in theneurotoxicity of6-OHDA, dopamine and MPTP: contribution to theapoptotic theory in Parkinson's disease [J]. Prog Neurobiol,2001,65(2):135-172
59Von Bohlen und Halbach O, Dermietzel R. Neurotransmitters andNeuromodulators. Wiley‐VCH Verlag GmbH, Weinheim,2002, pp.53-63
60Bortolato M, Chen K, Shih JC. Monoamine oxidase inactivation: frompathophysiology to therapeutics [J]. Adv Drug Deliv Rev,2008,60(13-14):1527-1533
61Sagud M, Mück-Seler D, Mihaljevi-Peles A, et al. Catechol-O-methyltransferase and schizophrenia [J]. Psychiatr Danub,2010,22(2):270-274
62Kebabian JW, Calne DB. Multiple receptors for dopamine [J]. Nature,1979,277(5692):93-96
63Missale C, Nash SR, Robinson SW, et al. Dopamine Receptors: FromStructure to Function [J]. Physiol Rev,1998,78(1):189-225
64Giros B, Sokoloff P, Martres MP, et al. Alternative splicing directs theexpression of two D2dopamine receptor isoforms [J]. Nature,1989,342(6265):923-926
65Probst WC, Snyder LA, Schuster DI. Sequence alignment of the G-proteincoupled receptor superfamily [J]. DNA Cell Biol,1992,11(1):1-20
66Noth R H, McCallum R W, CONTINO C, et al. Tonic dopaminergicsuppression of plasma aldosterone [J]. J Clin Endocrinol Metab,1980,51(1):64-69
67Greengard P, Allen PB, Nairn AC. Beyond the dopamine receptor: TheDARPP-32/protein phosphatase-1cascade [J]. Neuron,1999,23(3):435-447
68Grace AA. Dopamine. Neuropsychopharmacology: The Fifth Generationof Progress. Davis KL, Charney D, Coyle JT, Nemeroff C, New York,Lippincott Williams and Wilkins,2002, pp.119-132
69Harsing LG Jr, Zigmond MJ. Influence of dopamine on GABA release instriatum: Evidence for D1‐D2interactions and non‐synaptic influences[J]. Neuroscience,1997,77(2):419-429
70Jackson D M, Westlind-Danielsson A. Dopamine receptors: molecularbiology, biochemistry and behavioral aspects [J]. Pharmacol Ther,1994,64(2):291-369
71Diaz J, Lévesque D, Lammers CH, et al. Phenotypical characterization ofneurons expressing the dopamine D3receptor in the rat brain [J].Neuroscience,1995,65(3):731-745
72Bagdy E, Harsing LG Jr. The role of various calcium and potassiumchannels in the regulation of somatodendritic serotonin release [J].Neurochem Res,1995,20(12):1409-1415
73Zahm DS, Trimble M. The Dopaminergic Projection System, BasalForebrain Macrosystems, and Conditioned Stimuli [J]. Brain Regions ofInterest, CNS Spectr,2008,13(1):32-40
74Fallon JH, Koziell DA, Moore RY. Catecholamine innervation of the basalforebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex [J]. JComp Neurol,1978,180(3):509-532
75Fallon JH, Moore RY. Catecholamine innervation of the basal forebrain.IV. Topography of the dopamine projection to the basal forebrain andneostriatum [J]. J Comp Neurol,1978,180(3):545-580
76Swanson LW. The projections of the ventral tegmental area and adjacentregions: a combined fluorescent retrograde tracer andimmunoflourescence study in the rat [J]. Brain Res Bull,1982,9(1-6):321-353
77Fallon, JH. Topographic association of ascending dopaminergicprojections [J]. Ann N Y Acad Sci,1988,537:1-9
78Cooper JR, Bloom FE, Roth RH. Dopamine. The Biochemical Basis ofNeuropharmacology. Oxford University Press, New York,1996, pp.293-351
79Houk JC, Davis JL, Beiser DG, et al. Models of Information Processing inthe Basal Ganglia. Cambridge, Mass: MIT Press,1995
80Marsden CD. The mysterious motor function of the basal ganglia: TheRobert Wartenberg Lecture [J]. Neurology,1982,32(5):514-539
81Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson’sdisease [J]. Adv Neurol,1986,45:19-34
82Wise RA. Action of drugs of abuse on brain reward systems [J].Pharmacol Biochem Behav,1980,13(suppl1):213-223
83Huot P, Lévesque M, Parent A. The fate of striatal dopaminergic neuronsin Parkinson’s disease and Huntington’s chorea [J]. Brain,2007,130(pt1):222-232
84Rebec GV, Grabner CP, Johnson M, et al. Transient increases incatecholaminergic activity in medial prefrontal cortex and nucleusaccumbens shell during novelty [J]. Neuroscience,1997,76(3):707-714
85Schultz W, Dayan P, Montague PR. A neural substrate of prediction andreward [J]. Science,1997,275(5306):1593-1599
86Rommerts FFG. Testosterone:an overview of biosynthesis, transport,metabolism and action. In Nieschlag E and Berber HM.(eds.)Testosterone Action. Deficiency sub situation. Springer-verlag.1990,1-22
87Carson C III, Rittmaster R. The role of dihydrotestosterone in benignprostatic hyperplasia [J]. Urology,2003,61(4Suppl1):2-7
88Bullock LP. Brief Overview of Selected Aspects of Testicular HormoneAction [J]. Environ Health Perspect,1981,38:11-18
89Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes[J]. Sports Med,2004,34(8):513-554
90Bahrke MS, Yesalis CE, Brower KJ. Anabolic-androgenic steroid abuseand performance-enhancing drugs among adolescents [J]. Child AdolescPsychiatr Clin N Am,1998,7(4):821-838
91Clark AS, Henderson LP. Behavioral and physiological responses toanabolic-androgenic steroids [J]. Neurosci and Biobehav Rev,2003,27(5):413-436
92Kuhn CM. Anabolic steroids [J]. Rec Prog Horm Res,2002,57:411-434
93Andersen L, Goto-Kazeto R, Trant JM, et al. Short-term exposure to lowconcentrations of the synthetic androgen methyltestosterone affectsvitellogenin and steroid levels in adult male zebrafish (Danio rerio)[J].Aquat Toxicol,2006,76(3-4):343-352
94Mor G, Eliza M, Song J, et al.17α-methyltestosterone is a competitiveinhibitor of aromatase activity in Jar choriocarcinoma cells andmacrophage-like THP-1cells in culture [J]. J Ster Biochem Mol Biol,2001,79(1-5):239-246
95Schumacher M, Weill-Engerer S, Liere P, et al. Steroid hormones andneurosteroids in normal and pathological aging of the nervous system [J].Prog Neurobiol,2003,71(1):3-29
96Patchev VK, Schroeder J, Goetz F, et al. Neurotropic action of androgens:principles, mechanisms and novel targets [J]. Exp Gerontol,2004,39(11-12):1651-1660
97Putnam SK, Du J, Sato S, et al. Testosterone restoration of copulatorybehavior correlates with medial preoptic dopamine release in castratedmale rats [J]. Horm Behav,2001,39(3):216-224
98Putnam SK, Sato S, Hull EM. Effects of testosterone metabolites oncopulation and medial preoptic dopamine release in castrated male rats [J].Horm Behav,2003,44(5):419-426
99Kaminetsky JC. Benefits of a new testosterone gel formulation forhypogonadal men [J]. Clin Cornerstone,2005,7(Suppl4): S8-S12
100Frye CA, Edinger K, Sumida K. Androgen administration to aged malemice increases anti-anxiety behavior and enhances cognitive performance[J]. Neuropsychopharmacology,2008,33(5):1049-1061
101Aikey JL, Nyby JG, Anmuth JM, et al. Testosterone rapidly reducesanxiety in male house mice (Mus musculus)[J]. Horm Behav,2002,42(4):448-460
102Bitran D, Kellog CK, Hilvers RJ. Treatment with an anabolic-androgenicsteroid affects anxiety-related behavior and alters the sensitivity of corticalGABAA receptors in the rat [J]. Horm Behav,1993,27(4):568-583
103Frye CA, Seliga AM. Testosterone increases analgesia, anxiolysis, andcognitive performance of male rats [J]. Cogn Affect Behav Neurosci,2001,1(4):371-381
104Clark AS, Barber DM. Anabolic–androgenic steroids and aggression incastrated male rats [J]. Physiol Behav,1994,56(5):1107-1113
105Farrell SF, McGinnis MY. Effects of pubertal anabolic–androgenic steroid(AAS) administration on reproductive and aggressive behaviors in malerats [J]. Behav Neurosci,2003,117(5):904-911
106Breuer ME, McGinnis MY, Lumia AR, Possidente BP, et al.Aggression in male rats receiving anabolic androgenic steroids: effects ofsocial and environmental provocation [J]. Horm Behav,2001,40(3):409-418
107Martinez-Sanchis S, Salvador A, Moya-Albiol L, et al. Effects of chronictreatment with testosterone propionate on aggression and hormonal levelsin intact male mice [J]. Psychoneuroendocrinology,1998,23(3):275-293
108Bitran D, Kellog CK, Hilvers RJ. Treatment with an anabolic-androgenicsteroid affects anxiety-related behavior and alters the sensitivity of corticalGABAA receptors in the rat [J]. Horm Behav,1993,27(4):568-583
109Edinger KL, Frye CA. Testosterone's anti-anxiety and analgesic effectsmay be due in part to actions of its5alpha-reduced metabolites in thehippocampus [J]. Psychoneuroendocrinology,2005,30(5):418-430
110Minkin DM, Meyer ME, van Haaren F. Behavioral effects of long-termadministration of an anabolic steroid in intact and castrated male Wistarrats [J]. Pharmacol Biochem Behav,1993,44(4):959-963
111Adler A, Vescovo P, Robinson JK, et al. Gonadectomy in adult lifeincreases tyrosine hydroxylase immunoreactivity in the prefrontal cortexand decreases open field activity in male rats [J]. Neuroscience,1999,89(3):939-954
112Zhang G, Shi G, Tan H, et al. Intranasal administration of testosteroneincreased immobile-sniffing, exploratory behavior, motor behavior andgrooming behavior in rats [J]. Horm Behav,2011,59(4):477-483
113Uzych L. Anabolic–androgenic steroids and psychiatric-related effects: areview [J]. Can J Psychiatry,1992,37(1):23-28
114Hoberman JM, Yesalis CE. The history of synthetic testosterone [J]. SciAm,1995,272(2):76-81
115Williamson DJ, Young AH. Psychiatric effects of androgenic andanabolic-androgenic steroid abuse in men: a brief review of the literature[J]. J Psychopharmacol,1992,6(1):20-26
116Corrigan B. Anabolic steroids and the mind [J]. Med J Aust,1996,165(4):222-226
117Berning JM, Adams KJ, Stamford BA. Anabolic steroid usage in athletics:facts, fiction, and public relations [J]. J Strength Cond Res,2004,18(4):908-917
118Denham BE. Determinants of anabolic–androgenic steroid riskperceptions in youth populations: a multivariate analysis [J]. J Health SocBehav,2009,50(3):277-292
119Pope HG Jr, Katz DL. Psychiatric and medical effects ofanabolic-androgenic steroid use [J]. Arch Gen Psychiatry,1994,51(5):375-381
120Oliva CC, Middleton RK. Anabolic steroid-induced psychiatric reactions[J]. DICP,1990,24(4):388
121Galligani N, Renck A, Hansen S. Personality profile of men using anabolicandrogenic steroids [J]. Horm Behav,1996,30(2):170-175
122Olweus D, Mattsson A, Schalling D, et al. Circulating testosterone levelsand aggression in adolescent males: a causal analysis [J]. Psychosom Med,1988,50(3):261-272
123Vermes I, Várszegi M, Tóth EK, et al. Action of androgenic steroids onbrain neurotransmitters in rats [J]. Neuroendocrinology,1979,28(6):386-393
124Thiblin I, Finn A, Ross SB, et al. Increased dopaminergic and5-hydroxytryptaminergic activities in male rat brain following long-termtreatment with anabolic androgenic steroids [J]. Br J Pharmacol,1999,126(6):1301-1306
125Mitchell JB, Stewart J. Effects of castration, steroid replacement, andsexual experience on mesolimbic dopamine and sexual behaviors in themale rat [J]. Brain Res,1989,491(1):116-127
126de Souza Silva MA, Mattern C, Topic B, et al. Dopaminergic andserotonergic activity in neostriatum and nucleus accumbens enhanced byintranasal administration of testosterone [J]. Eur Neuropsychopharmacol,2009,19(1):53-63
127Koob G. Drugs of abuse: anatomy, pharmacology and function of rewardpathways [J]. Trends Pharmacol Sci,1992,13(5):177-184
128Kindlundh AM, Lindblom J, Nyberg F. Chronic administration withnandrolone decanoate induces alterations in the gene-transcript content ofdopamine D(1)-and D(2)-receptors in the rat brain [J]. Brain Res,2003,979(1-2):37-42
129Kindlundh A, Lindblom J, Bergstrom L, et al. The anabolic-androgenicsteroid nandrolone decanoate affects the density of dopamine receptors inthe male rat brain [J]. Eur J Neurosci,2001,13(2):291-296
130Gerfen CR, Engber TM, Mahan LC, et al. D1and D2dopaminereceptor-regulated gene expression of striatonigral and striatopallidalneurons[J]. Science,1990,250(4986):1429-1432
131Heimer L, Zahm DS, Churchill L, et al. Specificity in the projectionpatterns of accumbal core and shell in the rat [J]. Neuroscience,1991,41(1):89-125
132Koob GF. The neurobiology of addiction: a neuroadaptational viewrelevant for diagnosis [J]. Addiction,2006,101(Suppl1):23-30
133Dulawa SC, Grandy DK, Low MJ, et al. Dopamine D4receptor-knock-outmice exhibit reduced exploration of novel stimuli [J]. J Neurosci,1999,19(21):9550-9556
134Avale ME, Falzone TL, Gelman DM, et al. The dopamine D4receptor isessential for hyperactivity and impaired behavioral inhibition in a mousemodel of attention deficit/hyperactivity disorder [J]. Mol Psychiatry,2004,9(7):718-726
135Kindlundh AM, Bergstrom M, Monazzam A, et al. Dopaminergic effectsafter chronic treatment with nandrolone visualized in rat brain by positronemission tomography [J]. Prog Neuropsychopharmacol Biol Psychiatry,2002,26(7-8):1303-1308
136Kindlundh AM, Rahman S, Lindblom J, et al. Increased dopaminetransporter density in the male rat brain following chronic nandrolonedecanoate administration [J]. Neurosci Lett,2004,356(2):131-134
137Jaber M, Jones S, Giros B, et al. The dopamine transporter: a crucialcomponent regulating dopamine transmission [J]. Mov Disord,1997,12(5)629-633
138Abreu P, Hernandez G, Calzadilla CH, et al. Reproductive hormonescontrol striatal tyrosine hydroxylase activity in the male rat [J]. NeurosciLett,1988,95(1-3):213-217
139Cui R, Zhang G, Kang Y, et al. Amelioratory effects of testosteronepropionate supplement on behavioral, biochemical and morphologicalparameters in aged rats [J]. Exp Gerontol,2012,47(1):67-76
140Weltzien FA, Pasqualini C, Sebert ME, et al. Androgen-dependentstimulation of brain dopaminergic systems in the female European eel(Anguilla anguilla)[J]. Endocrinology,2006,147(6):2964-2973
141Dluzen DE, Ramirez VD. Effects of orchidectomy on nigro-striataldopaminergic function: behavioral and physiological evidence [J]. JNeuroendocrinol,1989,1(4):285-290
142Hernandez L, Gonzalez L, Murzi E, et al. Testosterone modulatesmesolimbic dopaminergic activity inmale rats [J]. Neurosci Lett,1994,171(1-2):172-174
143Long SF, Dennis LA, Russell RK, et al. Testosterone implantation reducesthe motor effects of cocaine [J]. Behav Pharmacol,1994,5(1):103-106
144Johnson ML, Day AE, Ho CC, et al. Androgen Decreases DopamineNeurone Survival in Rat Midbrain [J]. J Neuroendocrinol,2010,22(4):238-247
145Lumia AR, McGinnis MY. Impact of anabolic androgenic steroids onadolescent males [J]. Physiol Behav,2010,100(3):199-204
146Committee NRN. A unified nomenclature system for the nuclear receptorsuperfamily [J]. Cell,1999,97(2):161-163
147DonCarlos LL, Sarkey S, Lorenz B, et al. Novel cellular phenotypes andsubcellular sites for androgen action in the forebrain [J]. Neuroscience,2006,138(3):801-807
148Tsai MJ, O’Malley BW. Molecular mechanisms of action ofsteroid/thyroid receptor superfamily members [J]. Annu Rev Biochem,1994,63:451-486
149Beato M, Herrlich P, Schütz G. Steroid hormone receptors: many actors insearch of a plot [J]. Cell,1995,83(6):851-857
150Pike CJ, Nguyen TV, Ramsden M, et al. Androgen cell signaling pathwaysinvolved in neuroprotective actions [J]. Horm Behav,2008,53(5):693-705
151Gatson JW, Singh M. Activation of a membrane-associated androgenreceptor promotes cell death in primary cortical astrocytes [J].Endocrinology,2007,148(5):2458-2464
152Lin J, Adam RM, Santiestevan E, et al. The phosphatidylinositol3′-kinasepathway is a dominant growth factor-activated cell survival pathway inLNCaP human prostate carcinoma cells [J]. Cancer Res,1999,59(12):2891-2897
153Grewal SS, York RD, Stork PJ. Extracellular-signal-regulated kinasesignalling in neurons [J]. Curr Opin Neurobiol,1999,9(5):544-553
154Peterziel H, Mink S, Schonert A, et al. Rapid signalling by androgenreceptor in prostate cancer cells [J]. Oncogene,1999,18(46):6322-6329
155Pike CJ. Testosterone attenuates β-amyloid toxicity in culturedhippocampal neurons [J]. Brain Res,2001,919(1):160-165
156Corti O, Hampe C, Darios F, et al. Parkinson’s disease: from causes tomechanisms [J]. C R Biologies,2005,328(2):131-142
157Okun SM, McDonald WM, Delong MR. Refractory non-motor symptomsin male patients with Parkinson disease due to testosterone deficiency [J].Arch Neurol,2002,59(5):807-811
158Okun MS, Walter BL, McDonald WM, Tenover JL, Green J, Juncos JL,DeLong MR. Beneficial effects of testosterone replacement for thenonmotor symptoms of Parkinson disease [J]. Arch Neurol,2002,59(11):1750-1753
159Mitchell E, Thomas D, Burnet R. Testosterone improves motor function inParkinson’s disease [J]. J Clin Neurosci,2006,13(1):133-136
160Ekue A, Boulanger JF, Morissette M, et al. Lack of effect of testosteroneand dihydrotestosterone compared to17β-oestradiol in1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice [J]. JNeuroendocrinol,2002,14(9):731-736
161Cunningham RL, Macheda T, Watts LT, et al. Androgens exacerbate motorasymmetry in male rats with unilateral6-hydroxydopamine lesion [J].Horm Behav,2011,60(5):617-624