Dataset Information

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors.

ABSTRACT: 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 BDNFMet/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 GABAAR?3 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 BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/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.

SUBMITTER: Hao R

PROVIDER: S-EPMC5643500 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors.

Hao Rui R Qi Yu Y Hou Dong-Ni DN Ji Yuan-Yuan YY Zheng Chun-Yan CY Li Chu-Yu CY Yung Wing-Ho WH Lu Bai B Huang Ying Y

Frontiers in cellular neuroscience 20171012

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<sup>Met/Met</sup> mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. The ...[more]

PMID: 29075179

Similar Datasets

Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Dataset Information

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors.

Publications

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets