PMID- 29075179 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 11 DP - 2017 TI - BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors. PG - 306 LID - 10.3389/fncel.2017.00306 [doi] LID - 306 AB - Brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP) in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNF(Met/Met) mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABA(A)Rbeta3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD) induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNF(Met/Met) mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNF(Met/Met) mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers. FAU - Hao, Rui AU - Hao R AD - Laboratory of Neuronal Circuit & Neuroplasticity, Department of Neurology, Tongji Hospital, Shanghai, China. AD - Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai, China. AD - Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Qi, Yu AU - Qi Y AD - Laboratory of Neuronal Circuit & Neuroplasticity, Department of Neurology, Tongji Hospital, Shanghai, China. AD - Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai, China. AD - Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Hou, Dong-Ni AU - Hou DN AD - Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Ji, Yuan-Yuan AU - Ji YY AD - Neurodegeneration Discovery Performance Unit, GlaxoSmithKline (China) R&D, Shanghai, China. FAU - Zheng, Chun-Yan AU - Zheng CY AD - Neurodegeneration Discovery Performance Unit, GlaxoSmithKline (China) R&D, Shanghai, China. FAU - Li, Chu-Yu AU - Li CY AD - Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Yung, Wing-Ho AU - Yung WH AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. FAU - Lu, Bai AU - Lu B AD - School of Pharmaceutical Sciences, Tsinghua University, Beijing, China. FAU - Huang, Ying AU - Huang Y AD - Laboratory of Neuronal Circuit & Neuroplasticity, Department of Neurology, Tongji Hospital, Shanghai, China. AD - Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai, China. AD - Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171012 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 EIN - Front Cell Neurosci. 2017 Nov 13;11:351. PMID: 29219152 PMC - PMC5643500 OTO - NOTNLM OT - 5-HT3 receptors OT - BDNF val66met polymorphism OT - LTD OT - hippocampus OT - synaptic plasticity EDAT- 2017/10/28 06:00 MHDA- 2017/10/28 06:01 PMCR- 2017/01/01 CRDT- 2017/10/28 06:00 PHST- 2017/04/13 00:00 [received] PHST- 2017/09/13 00:00 [accepted] PHST- 2017/10/28 06:00 [entrez] PHST- 2017/10/28 06:00 [pubmed] PHST- 2017/10/28 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2017.00306 [doi] PST - epublish SO - Front Cell Neurosci. 2017 Oct 12;11:306. doi: 10.3389/fncel.2017.00306. eCollection 2017.