研究组在美国《分子精神病学》发表题为“Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin”的文章。
Molecular Psychiatry advance online publication, 5 August 2014; doi:10.1038/mp.2014.75
Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin.
X Wang1,2, D Zhang2 and X-Y Lu2
Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China and 2Department of Pharmacology, The University of Texas Health
Science Center at San Antonio, San Antonio, TX, USA. Correspondence: Dr X-Y Lu, Department of Pharmacology, The University of Texas Health Science Center at San Antonio,
7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
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 inbehavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamaterelease 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 NMDAblocked 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.Molecular Psychiatry advance online publication, 5 August 2014; doi:10.1038/mp.2014.75.