压力耐受大鼠和压力易感大鼠大脑白质及白质内有髓神经纤维的体视学研究
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摘要
目的探讨在慢性不可预知性应激(chronic unpredictable stress,CUS)后压力耐受大鼠大脑白质体积及白质内有髓神经纤维总体积的改变,分析对压力的耐受能力是否与大脑白质的改变有关。方法选用50只4~5周龄雄性Sprague-Dawley(SD)大鼠,采用完全随机法分为空白对照组和模型组。模型组的大鼠在给予4周的CUS之后,根据糖水偏好实验(sucrose preference test,SPT)的结果筛选出压力易感组和压力耐受组。采用旷场实验(open field test,OFT)评估各组的行为学水平,运用体视学方法计算各组大鼠白质体积和白质内有髓神经纤维的体积。结果压力易感组的蔗糖偏好百分比显著低于空白对照组和压力耐受组(P<0.01)。压力耐受组OFT总成绩显著优于空白对照组和压力易感组(P<0.01)。压力耐受组的白质体积显著性高于压力易感组(P<0.01),但与空白对照组比较,差异没有统计学意义(P>0.05)。压力耐受组白质的有髓神经纤维总体积显著性高于压力易感组(P<0.01),与空白对照组相比差异没有统计学意义(P>0.05)。结论白质和白质内有髓神经纤维的改变可能与抑郁易感性差异存在关系。
Objective To investigate the changes in the total volume of the white matter and the myelinated nerve fibers in the white matter of stress-resilient rats after chronic unpredictable stress( CUS) and explore whether resilience to stress is related to white matter changes. Methods Fifty 4-to 5-week-old male Sprague-Dawley rats were randomized into the control group and CUS group. The rats in CUS group were exposed to a 4-week CUS,and the stress-susceptible and stress-resilient rats were screened using sucrose preference test. The behavioral changes of the rats were assessed using open field test. In each rat,the white matter volume and the total volume of the myelinated nerve fibers in the white matter were investigated using stereological methods. Results The stress-susceptible rats showed significantly lowered sucrose preference compared with the control rats and stress-resilient rats( P < 0. 01). The stress-resilient rats had significantly higher total scores in open field test than the control and stress-susceptible rats( P < 0. 01). The white matter volume of the stress-resilient rats was significantly greater than that of the stress-susceptible rats( P < 0. 01)and was similar to that in the control rats( P > 0. 05). The total volume of the myelinated nerve fibers in the white matter of the stress-resilient rats was higher than that of the stress-susceptible rats( P < 0. 01) but similar to that of the control rats( P > 0. 05). Conclusion The changes in the white matter and the myelinated nerve fibers in the white matter might be associated with the differences in the susceptibility to depression.
Objective To investigate the changes in the total volume of the white matter and the myelinated nerve fibers in the white matter of stress-resilient rats after chronic unpredictable stress( CUS) and explore whether resilience to stress is related to white matter changes. Methods Fifty 4-to 5-week-old male Sprague-Dawley rats were randomized into the control group and CUS group. The rats in CUS group were exposed to a 4-week CUS,and the stress-susceptible and stress-resilient rats were screened using sucrose preference test. The behavioral changes of the rats were assessed using open field test. In each rat,the white matter volume and the total volume of the myelinated nerve fibers in the white matter were investigated using stereological methods. Results The stress-susceptible rats showed significantly lowered sucrose preference compared with the control rats and stress-resilient rats( P < 0. 01). The stress-resilient rats had significantly higher total scores in open field test than the control and stress-susceptible rats( P < 0. 01). The white matter volume of the stress-resilient rats was significantly greater than that of the stress-susceptible rats( P < 0. 01)and was similar to that in the control rats( P > 0. 05). The total volume of the myelinated nerve fibers in the white matter of the stress-resilient rats was higher than that of the stress-susceptible rats( P < 0. 01) but similar to that of the control rats( P > 0. 05). Conclusion The changes in the white matter and the myelinated nerve fibers in the white matter might be associated with the differences in the susceptibility to depression.
引文
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[31]KIESEPP T,EEROLA M,M NTYL R,et al.Major depressive disorder and white matter abnormalities:a diffusion tensor imaging study with tract-based spatial statistics[J].J Affect Disord,2010,120(1-3):240-244.DOI:10.1016/j.jad.2009.04.023.
[32]LI W,MUFTULER L T,CHEN G,et al.Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure[J].J Neurol Sci,2014,338(1/2):46-56.DOI:10.1016/j.jns.2013.12.016.
[2]COHEN S,JANICKI-DEVERTS D,MILLER G E.Psychological stress and disease[J].JAMA,2007,298(14):1685-1687.DOI:10.1001/jama.298.14.1685.
[3]KIRTON J W,RESNICK S M,DAVATZIKOS C,et al.Depressive symptoms,symptom dimensions,and white matter lesion volume in older adults:a longitudinal study[J].Am J Geriatr Psychiatry,2014,22(12):1469-1477.DOI:10.1016/j.jagp.2013.10.005.
[4]BERGAMINO M,KUPLICKI R,VICTOR T A,et al.Comparison of two different analysis approaches for DTI free-water corrected and uncorrected maps in the study of white matter microstructural integrity in individuals with depression[J].Hum Brain Mapp,2017,38(9):4690-4702.DOI:10.1002/hbm.23694.
[5]GAO Y,MA J,TANG J,et al.White matter atrophy and myelinated fiber disruption in a rat model of depression[J].J Comp Neurol,2017,525(8):1922-1933.DOI:10.1002/cne.24178.
[6]YUEN T J,SILBEREIS J C,GRIVEAU A,et al.Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis[J].Cell,2014,158(2):383-396.DOI:10.1016/j.cell.2014.04.052.
[7]THAM M W,WOON P S,SUM M Y,et al.White matter abnormalities in major depression:evidence from post-mortem,neuroimaging and genetic studies[J].J Affect Disord,2011,132(1-2):26-36.DOI:10.1016/j.jad.2010.09.013.
[8]MATTHEWS S C,STRIGO I A,SIMMONS A N,et al.A multimodal imaging study in U.S.veterans of Operations Iraqi and Enduring Freedom with and without major depression after blast-related concussion[J].Neuroimage,2011,54(Suppl1):S69-S75.DOI:10.1016/j.neuroimage.2010.04.269.
[9]GALINOWSKI A,MIRANDA R,LEMAITRE H,et al.Resilience and corpus callosum microstructure in adolescence[J].Psychol Med,2015,45(11):2285-2294.DOI:10.1017/S0033291715000239.
[10]LI C,YANG S,CHEN L,et al.Stereological methods for estimating the myelin sheaths of the myelinated fibers in white matter[J].Anat Rec(Hoboken),2009,292(10):1648-1655.DOI:10.1002/ar.20959.
[11]WILLNER P,TOWELL A,SAMPSON D,et al.Reduction of sucrose preference by chronic unpredictable mild stress,and its restoration by a tricyclic antidepressant[J].Psychopharmacology(Berl),1987,93(3):358-364.DOI:10.1007/bf00187257.
[12]KIM C S,BRAGER D H,JOHNSTON D.Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress[J].Mol Psychi,2017.DOI:10.1038/mp.2017.28.
[13]ZURAWEK D,KUSMIDER M,FARON-GORECKA A,et al.Reciprocal microRNA expression in mesocortical circuit and its interplay with serotonin transporter define resilient rats in the chronic mild stress[J].Mol Neurobiol,2017,54(8):5741-5751.DOI:10.1007/s12035-016-0107-9.
[14]KATZ R J.Animal model of depression:pharmacological sensitivity of a hedonic deficit[J].Pharmacol Biochem Behav,1982,16(6):965-968.DOI:10.1016/0091-3057(82)90053-3.
[15]LIU J,DIETZ K,DELOYHT J M,et al.Impaired adult myelination in the prefrontal cortex of socially isolated mice[J].Nat Neurosci,2012,15(12):1621-1623.DOI:10.1038/nn.3263.
[16]TANG Y,NYENGAARD J R,PAKKENBERG B,et al.Age-induced white matter changes in the human brain:a stereological investigation[J].Neurobiol Aging,1997,18(6):609-615.DOI:10.1016/s0197-4580(97)00155-3.
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[19]CHAUDHURY D,WALSH J J,FRIEDMAN A K,et al.Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons[J].Nature,2013,493(7433):532-536.DOI:10.1038/nature11713.
[20]FRIEDMAN A K,WALSH J J,JUAREZ B,et al.Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience[J].Science,2014,344(6181):313-319.DOI:10.1126/science.1249240.
[21]HERRERA-P REZ J J,MART NEZ-MOTA L,CHAVIRA R,et al.Testosterone prevents but not reverses anhedonia in middle-aged males and lacks an effect on stress vulnerability in young adults[J].Horm Behav,2012,61(4):623-630.DOI:10.1016/j.yhbeh.2012.02.015.
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[25]KAUTZ M,CHARNEY D S,MURROUGH J W.Neuropeptide Y,resilience,and PTSD therapeutics[J].Neurosci Lett,2017,649:164-169.DOI:10.1016/j.neulet.2016.11.061.
[26]SUN H,SU R,ZHANG X,et al.Hippocampal GR-and CB1-mediated m GluR5 differentially produces susceptibility and resilience to acute and chronic mild stress in rats[J].Neuroscience,2017,357:295-302.DOI:10.1016/j.neuroscience.2017.06.017.
[27]FEBBRARO F,SVENNINGSEN K,TRAN T P,et al.Neuronal substrates underlying stress resilience and susceptibility in rats[J].PLo S ONE,2017,12(6):e0179434.DOI:10.1371/journal.pone.0179434.
[28]WORLEY N B,HILL M N,CHRISTIANSON J P.Prefrontal endocannabinoids,stress controllability and resilience:A hypothesis[J].Prog Neuro Psychopharmacol Biol Psychiatry,2017.DOI:10.1016/j.pnpbp.2017.04.004.
[29]BALLMAIER M,TOGA A W,BLANTON R E,et al.Anterior cingulate,gyrus rectus,and orbitofrontal abnormalities in elderly depressed patients:an MRI-based parcellation of the prefrontal cortex[J].Am J Psychiatry,2004,161(1):99-108.DOI:10.1176/appi.ajp.161.1.99.
[30]HEMANTH KUMAR B S,MISHRA S K,TRIVEDI R,et al.Demyelinating evidences in CMS rat model of depression:a DTI study at 7 T[J].Neuroscience,2014,275:12-21.DOI:10.1016/j.neuroscience.2014.05.037.
[31]KIESEPP T,EEROLA M,M NTYL R,et al.Major depressive disorder and white matter abnormalities:a diffusion tensor imaging study with tract-based spatial statistics[J].J Affect Disord,2010,120(1-3):240-244.DOI:10.1016/j.jad.2009.04.023.
[32]LI W,MUFTULER L T,CHEN G,et al.Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure[J].J Neurol Sci,2014,338(1/2):46-56.DOI:10.1016/j.jns.2013.12.016.