Xiangzhi Jiang1, Wei Lin2, Yuanyuan Cheng3, Dongming Wang4. 1. Psychiatric Outpatient, Qingdao Mental Health Center, Qingdao, China. 2. Open Mental Department, Qingdao Mental Health Center, Qingdao, China. 3. Psychosis Department Ⅰ, Qingdao Mental Health Center, Qingdao, China. 4. Old Age Psychosis Department Ⅱ, Qingdao Mental Health Center, Qingdao, China.
Abstract
BACKGROUND: Glutamatergic system has been known to play a role in the pathogenesis of major depression disorder by inducing N-methyl-d-aspartate receptor-dependent long-term depression (LTD) or metabotropic glutamate receptors (mGluR)-dependent LTD. Here, we characterized the LTD in a chronic social defeat stress (CSDS)-induced depressive mouse model. METHODS: CSDS was used to induce the depressive-like behaviors in C57BL/6 male mice, which were assessed using sucrose preference test and social interaction test. The synaptic strength including LTD and long-term potentiation (LTP) induced by paired-pulse low frequency stimulation (PP-LFS) was measured using whole-cell recording technique. RESULTS: CSDS induced depressive-like behaviors and facilitated PP-LFS-induced LTD in hippocampal CA3-CA1 pathway in the susceptible mice. Interestingly, mGluR5 but not N-methyl-d-aspartate receptor mediated the PP-LFS-induced LTD. In addition, mGluR5 agonist dihydroxyphenylglycine promoted PP-LFS-induced LTD specifically in susceptible mice, which was diminished by activating the BDNF/TrkB signaling pathway. CONCLUSIONS: Our results suggest that mGluR5-dependent LTD might be responsible for the development of depressive-like behaviors in CSDS-induced depression mice model.
BACKGROUND: Glutamatergic system has been known to play a role in the pathogenesis of major depression disorder by inducing N-methyl-d-aspartate receptor-dependent long-term depression (LTD) or metabotropic glutamate receptors (mGluR)-dependent LTD. Here, we characterized the LTD in a chronic social defeat stress (CSDS)-induced depressivemouse model. METHODS: CSDS was used to induce the depressive-like behaviors in C57BL/6 male mice, which were assessed using sucrose preference test and social interaction test. The synaptic strength including LTD and long-term potentiation (LTP) induced by paired-pulse low frequency stimulation (PP-LFS) was measured using whole-cell recording technique. RESULTS: CSDS induced depressive-like behaviors and facilitated PP-LFS-induced LTD in hippocampal CA3-CA1 pathway in the susceptible mice. Interestingly, mGluR5 but not N-methyl-d-aspartate receptor mediated the PP-LFS-induced LTD. In addition, mGluR5 agonist dihydroxyphenylglycine promoted PP-LFS-induced LTD specifically in susceptible mice, which was diminished by activating the BDNF/TrkB signaling pathway. CONCLUSIONS: Our results suggest that mGluR5-dependent LTD might be responsible for the development of depressive-like behaviors in CSDS-induced depressionmice model.
Authors: Lisa S Rotenstein; Marco A Ramos; Matthew Torre; J Bradley Segal; Michael J Peluso; Constance Guille; Srijan Sen; Douglas A Mata Journal: JAMA Date: 2016-12-06 Impact factor: 56.272
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