重复经颅直流电刺激对帕金森病模型大鼠抑郁行为的改善作用及其机制

doi:10.13481/j.1671-587x.20180401

摘要/Abstract

摘要： 目的：探讨重复经颅直流电刺激（tDCS）对帕金森病（PD）模型大鼠抑郁行为的影响，初步阐明tDCS影响PD相关抑郁行为的部分神经化学机制。方法：32只大鼠随机分为假手术组、PD组、阳极重复tDCS组和阴极重复tDCS组，每组8只，除假手术组外，其余各组大鼠制备PD模型。采用行为学方法观察各组大鼠在强迫游泳实验中的不动时间和蔗糖偏好实验中的蔗糖消耗量；采用高效液相色谱-电化学法观察各组大鼠大脑内侧前额叶皮质（mPFC）和中缝核（RN）中单胺类递质水平。结果：与PD组比较，阳极重复tDCS组和阴极重复tDCS组大鼠的不动时间均明显缩短（P<0.05或P<0.01），阳极重复tDCS组大鼠蔗糖消耗量明显增加（P<0.05），而阴极重复tDCS组大鼠蔗糖消耗量无明显变化（P>0.05）；阳极重复tDCS组大鼠mPFC和RN中多巴胺（DA）和5-羟色胺（5-HT）水平明显升高（mPFC：P<0.05或P<0.01；RN：P<0.01），阴极重复tDCS组大鼠仅mPFC中5-HT水平明显升高（P<0.05）。结论：重复tDCS能改善PD大鼠的抑郁行为，阳极重复tDCS的改善作用更为明显，其机制可能与相关脑区中单胺类递质水平升高有关联。

关键词: 重复经颅直流电刺激, 帕金森病, 抑郁, 单胺类

Abstract: Objective:To explore the effects of repeated transcranial direct current stimulation (tDCS) on the depression behaviors in the rat models of Parkinson' s disease (PD),and to clarify the neurochemical mechanism of tDCS in affecting the PD-related depression behaviors. Methods:A total of 32 rats were randomly divided into sham operation group,PD group,anodal repeated tDCS group and cathodal repeated tDCS group,8 rats in each group.Except sham operation group,the rats in other groups were used to establish the PD models.The depression behaviors immobility time and sucrose consumption of the rats in various groups were observed by forced swimming test and sucrose preference test.The monoamine levels in medial prefrontal cortex (mPFC) and raphe nuclei (RN) of the rats in various groups were assessed by HPLC-electrochemistry method. Results: Compared with PD group,the immobility time in anodal repeated tDCS group and cathodal repeated group was significantly decreased (P<0.05 or P<0.01);the sucrose consumption in anodal repeated tDCS group was significantly increased (P<0.05),but no significant change was observed in cathodal repeated tDCS group (P>0.05).Compared with PD group,the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in mPFC and RN of the rats in anodal repeated tDCS group were significantly increased(mPFC:P<0.05 or P <0.01; RN:P<0.01); the level of 5-HT in mPFC of the rats in cathodal repeated tDCS group was significantly increased (P<0.05). Conclusion:The repeated tDCS,especially the anodal repeated tDCS,can alleviate the depression behaviors in the rat models of PD,and their mechanisms may be related to the increasing of the monoamine levels in the related brain regions.

Key words: monoamine, repeated transcranial direct current stimulation, Parkinson’s disease, depression

中图分类号:

R338.6

王春雷, 常永丽, 韩玲娜. 重复经颅直流电刺激对帕金森病模型大鼠抑郁行为的改善作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(04): 693-697.

WANG Chunlei, CHANG Yongli, HAN Lingna. Improvement effects of repeated transcranial direct current stimulation on depression behaviors in rat models of Parkinson's disease and their mechanisms[J]. Journal of Jilin University Medicine Edition, 2018, 44(04): 693-697.

参考文献

[1] Kornreich C,Cole P,Kajosch H.Transcranial direct current stimulation (tDCS):psychiatric use[J].Rev Med Brux,2018,39(1):47-49.
[2] Csifcsák G,Boayue NM,Puonti O,et al.Effects of transcranial direct current stimulation for treating depression:A modeling study[J].J Affect Disord,2018,234:164-173.
[3] Bindman LJ,Lippold OC,Redfearn JW.The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects[J].J Physiol(Lond),1964,172:369-382.
[4] Nikolin S,Huggins C,Martin D,et al.Safety of repeated sessions of transcranial direct current stimulation:A systematic review[J].Brain Stimul,2018,11(2):278-288.
[5] Remy P,Doder M,Lees A,et al.Depression in Parkinson's disease:loss of dopamine and noradrenaline innervation in the limbic system[J].Brain,2005,128(Pt6):1314-1322.
[6] 俞雪鸿,田学隆,李一言,等.重复经颅直流电刺激帕金森病模型大鼠的旋转行为[J].中国组织工程研究,2012,16(24):4471-4475.
[7] Hadoush H,Al-Jarrah M,Khalil H,et al.Bilateral anodal transcranial direct current stimulation effect on balance and fearing of fall in patient with Parkinson's disease[J].Neuro Rehabilitation,2018,42(1):63-68.
[8] Dundas JE,Thickbroom GW,Mastaglia FL.Perception of comfort during transcranial DC stimulation:Effect of NaCl solution concentration applied to sponge electrodes[J].Clin Neurophysiol,2007,118(5):1166-1170.
[9] Liebetanz D,Koch R,Mayenfels S,et al.Safety limits of cathodal transcranial direct current stimulation in rats[J].Clin Neurophysiol,2009,120(6):1161-1167.
[10] Porsolt RD,Anton G,Blavet N,et al.Behavioural despair in rats:a new model sensitive to antidepressant treatments[J].Eur J Pharmacol,1978,47(4):379-391.
[11] Treadway MT,Zald DH.Reconsidering anhedonia in depression:lessons from translational neuroscience[J].Neurosci Biobrhav Rev,2011,35(3):537-555.
[12] Braak H,Del Tredici K,Rüb U,et al.Staging of brain pathology related to sporadic Parkinson's disease[J].Neurobiol Aging,2003,24(2):197-211.
[13] Löhle M,Storch A,Reichmann H.Beyond tremor and rigidity:non-motor features of Parkinson's disease[J].J Neural Transm(Vienna),2009,116(11):1483-1492.
[14] Han LN,Zhang L,Li LB,et al.Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat[J].Neuropharmacology,2015,93:68-79.
[15] Zanão TA,Moffa AH,Shiozawa P,et al.Impact of two or less missing treatment sessions on tDCS clinical efficacy:results from a factorial,randomized,controlled trial in major depression[J].Neuromodulation,2014,17(8):737-742.
[16] Liu S,Sheng J,Li B,et al.Recent advances in non-invasive brain stimulation for major depressive disorder[J].Front Hum Neurosci,2017,11:526.
[17] Kalu UG,Sexton CE,Loo CK,et al.Transcranial direct current stimulation in the treatment of major depression:a meta-analysis[J].Psychol Med,2012,42(9):1791-1800.
[18] Player MJ,Taylor JL,Weickert CS,et al.Increase in PAS-induced neuroplasticity after a treatment course of transcranial direct current stimulation for depression[J].J Affect Disord,2014,167:140-147.
[19] Pittenger C,Duman RS.Stress,depression,and neuroplasticity:a convergence of mechanisms[J].Neuropsychopharmacology,2008,33(1):89-109.
[20] 刘椰,姜依凡,刘鑫,等.背侧海马齿状回5-HT1A受体在帕金森病大鼠焦虑行为中的作用[J].西安交通大学学报:医学版,2017,38(3):402-409.