α7神经型尼古丁受体激动剂PNU282987对小鼠海马组织突触相关蛋白的影响
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摘要
目的探讨特异性激动小鼠α7神经型尼古丁受体(α7n AChR)水平对海马组织中突触相关蛋白表达的影响。方法选取6月龄非转基因C57雄性小鼠32只,随机分为对照组(Control),腹腔注射0.5、1.0 mg/kg、3.0 mg/kg PNU282987组各8只。采用Real-time PCR法和蛋白免疫印迹(Western印迹)法分别测定小鼠海马组织中囊泡相关蛋白突触素(Syn)、突触小体相关蛋白(SNAP)-25和突触后致密物(PSD)-95 mRNA及蛋白表达水平的变化。结果与对照组相比,1.0 mg/kg PNU282987组、3.0 mg/kg PNU282987组中突触相关蛋白Syn、PSD-95、SNAP-25的mRNA和蛋白表达水平均显著增高。结论特异性激动小鼠α7n AChR能够使海马组织中突触相关蛋白水平表达增加。这可能提示了α7n AChR与突触密切相关,这可能与其神经保护作用有关。
Objective To investigate the effect of specially agonism 7 neural nicotinic acetylcholine receptors( n AChR) in mouse on the expression of tissue synapse associated proteins( TSAPs),for better understanding of the neuroprotective role of 7 n AChR.Methods Thirty-two male non-transgenic C57 male mice were randomly divided into control,0. 5 mg/kg PNU282987,1. 0 mg/kg PNU282987,3.0 mg/kg PNU282987 groups. mRNA and protein expression levels of synaptophysin,SNAP-25,PSD-95 in mouse hippocampus were measured by Real-time PCR and Western blot respectively. Results Compared with the control group,the mRNA and protein levels of synaptic proteins Syn,PSD-95,SNAP-25 were significantly increased in 1 mg/kg PNU282987 and 3.0 mg/kg PNU282987 groups.Conclusions Stimulating the expression of α7 n AChR in mouse could raise the expression of hippocampus TSAPs,which suggests that α7 n AChR is closely related to the synaptic,which may be related to its neuroprotective effects.
Objective To investigate the effect of specially agonism 7 neural nicotinic acetylcholine receptors( n AChR) in mouse on the expression of tissue synapse associated proteins( TSAPs),for better understanding of the neuroprotective role of 7 n AChR.Methods Thirty-two male non-transgenic C57 male mice were randomly divided into control,0. 5 mg/kg PNU282987,1. 0 mg/kg PNU282987,3.0 mg/kg PNU282987 groups. mRNA and protein expression levels of synaptophysin,SNAP-25,PSD-95 in mouse hippocampus were measured by Real-time PCR and Western blot respectively. Results Compared with the control group,the mRNA and protein levels of synaptic proteins Syn,PSD-95,SNAP-25 were significantly increased in 1 mg/kg PNU282987 and 3.0 mg/kg PNU282987 groups.Conclusions Stimulating the expression of α7 n AChR in mouse could raise the expression of hippocampus TSAPs,which suggests that α7 n AChR is closely related to the synaptic,which may be related to its neuroprotective effects.
引文
1欧阳凯,齐晓岚,官志忠.神经型尼古丁乙酰胆碱受体在阿尔茨海默病中的神经保护作用[J].中国老年学杂志,2012;32(3):653-6.
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11 谢冰雪,张桂森,张亮仁.以α7 n AChR为靶点的药物研究进展[J].中国药物化学杂志,2015;(4):313-23.
12 Beinat C,Reekie T,Banister SD,et al.Structure-activity relationship studies of SEN12333 analogues:Determination of the optimal requirements for binding affinities atα7 n AChRs through incorporation of known structural motifs[J].Eur J Med Chem,2015;95(3):277-301.
13 Chan WK,Wong PT,Sheu FS.Frontal cortical alpha7 and alpha4beta2nicotinic acetylcholine receptors in working and reference memory[J].Neuropharmacology,2007;52(8):1641-9.
14 Toyohara J,Hashimoto K.α7 Nicotinic receptor agonists:potential therapeutic drugs for treatment of cognitive impairments in schizophrenia and Alzheimer's disease[J].Open Med Chem J,2010;4(2):37-56.
15 Vicens P,Ribes D,Heredia L,et al.Motor and anxiety effects of PNU-282987,an alpha7 nicotinic receptor agonist,and stress in an animal model of Alzheimer's disease[J].Curr Alzheimer Res,2013;10(5):516-23.
16 Wang DB,Kinoshita Y,Kinoshita C,et al.Loss of endophilinB1exacerbates Alzheimer's disease pathology[J].Brain,2015;138(Pt7):2005-19.
17 Guo HD,Tian JX,Zhu J,et al.Electroacupuncture suppressed neuronal apoptosis and improved cognitive impairment in the AD model rats possibly via downregulation of notch signaling pathway[J].Evid Based Compl Alte Med,2015;2015:393569.
18 Duman RS,Aghajanian GK.Synaptic dysfunction in depression:potential therapeutic targets[J].Science,2012;338(6103):68-72.
2 Huang X,Cheng Z,Su Q,et al.Neuroprotection by nicotine against colchicine-induced apoptosis is mediated by PI3-kinase-Akt pathways[J].INT J Neurosci,2012;122(6):324-32.
3 Lotfipour S,Mandelkern M,Brody AL.Quantitative molecular imaging of neuronal nicotinic acetylcholine receptors in the human brain with a-85380 radiotracers[J].Curr Med Imaging Rev,2011;7(2):107.
4 王昊飞.α7胆碱能受体激动剂DMXB对Aβ损伤认知功能的影响及其分子机制[D].南京:南京医科大学,2009.
5 Posadas I,López-Hernández B,Ce1a V.Nicotinic receptors in neurodegeneration[J].Curr Neuropharmacol,2013;11(3):298-314.
6 Qi XL,Ou-Yang K,Ren JM,et al.Preventing expression of the nicotinic receptor subunitα7 in SH-SY5Y cells with interference RNA indicates that this receptor may protect against the neurotoxicity of Aβ[J].Neurochem Res,2013;38(5):943-50.
7 Conejero-Goldberg C,Davies P,Ulloa L.Alpha7 nicotinic acetylcholine receptor:a link between inflammation and neurodegeneration[J].Neurosci Biobehav Rev,2008;32(4):693-706.
8 Nordman JC,Philips WS,Kodama N,et al.Axon targeting of the alpha 7nicotinic receptor in developing hippocampal neurons by Gprinl regulates growth[J].J Neurochem,2014;129(4):649-62.
9 D'Andrea MR,Nagele RG.Targeting the alpha7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer's disease pyramidal neurons[J].Curr Pharm Des,2006;12(6):677-84.
10 Ma L,Turner D,Zhang J,et al.Deficits of synaptic functions in hippocampal slices prepared from aged mice nullα7 nicotinic acetylcholine receptors[J].Neurosci Lett,2014;570(1):97-101.
11 谢冰雪,张桂森,张亮仁.以α7 n AChR为靶点的药物研究进展[J].中国药物化学杂志,2015;(4):313-23.
12 Beinat C,Reekie T,Banister SD,et al.Structure-activity relationship studies of SEN12333 analogues:Determination of the optimal requirements for binding affinities atα7 n AChRs through incorporation of known structural motifs[J].Eur J Med Chem,2015;95(3):277-301.
13 Chan WK,Wong PT,Sheu FS.Frontal cortical alpha7 and alpha4beta2nicotinic acetylcholine receptors in working and reference memory[J].Neuropharmacology,2007;52(8):1641-9.
14 Toyohara J,Hashimoto K.α7 Nicotinic receptor agonists:potential therapeutic drugs for treatment of cognitive impairments in schizophrenia and Alzheimer's disease[J].Open Med Chem J,2010;4(2):37-56.
15 Vicens P,Ribes D,Heredia L,et al.Motor and anxiety effects of PNU-282987,an alpha7 nicotinic receptor agonist,and stress in an animal model of Alzheimer's disease[J].Curr Alzheimer Res,2013;10(5):516-23.
16 Wang DB,Kinoshita Y,Kinoshita C,et al.Loss of endophilinB1exacerbates Alzheimer's disease pathology[J].Brain,2015;138(Pt7):2005-19.
17 Guo HD,Tian JX,Zhu J,et al.Electroacupuncture suppressed neuronal apoptosis and improved cognitive impairment in the AD model rats possibly via downregulation of notch signaling pathway[J].Evid Based Compl Alte Med,2015;2015:393569.
18 Duman RS,Aghajanian GK.Synaptic dysfunction in depression:potential therapeutic targets[J].Science,2012;338(6103):68-72.