齿状回CA3谷氨酸释放/NDMA传递介导抑郁患者的行为修复和瘦素的抗抑郁样反应

Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin
2015-04-29 10:12点击:262次发表评论
作者:Wang, X., Zhang, D., Lu, X.-Y.
机构: 滨州医学院代谢和神经精神疾病研究所
期刊: MOL PSYCHIATR2015年4月4期20卷

Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of glutamate release/transmission in behavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamate release and behavioral responses to tail suspension, a procedure commonly used for inducing behavioral despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in glutamate release in hippocampal field CA3, which declined gradually after its offset. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by intra-CA3 infusion of MK-801, a non-competitive NMDA receptor antagonist, reversed behavioral despair. A subpopulation of granule neurons that innervated the CA3 region expressed leptin receptors and these cells were not activated by stress. Leptin treatment dampened tail suspension-evoked glutamate release in CA3. On the other hand, intra-CA3 infusion of NMDA blocked the antidepressant-like effect of leptin in reversing behavioral despair in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Taken together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating behavioral despair and antidepressant-like responses to leptin. © 2015 Macmillan Publishers Limited All rights reserved.
 

通讯机构: Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China
学科代码:精神病学 基础医学   关键词:CA3谷氨酸;抑郁患者;抗抑郁; ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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