| First Author | Hao R | Year | 2017 |
| Journal | Front Cell Neurosci | Volume | 11 |
| Pages | 306 | PubMed ID | 29075179 |
| Mgi Jnum | J:276870 | Mgi Id | MGI:6307400 |
| Doi | 10.3389/fncel.2017.00306 | Citation | Hao R, et al. (2017) BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors. Front Cell Neurosci 11:306 |
| abstractText | 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 GABAARbeta3 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. |
