Food restriction alone, exercise alone or the two combined during adolescence rescue the behavioral deficits resulting from variant BDNF Val66Met polymorphism
Chen YW, Lee F, Aoki CJ
Society for Neuroscience. 2016.
Brain-derived neurotrophic factor (BDNF) is an important determinant of hippocampal function throughout the lifespan, facilitating neuronal survival and differentiation, synaptic structure and plasticity, long-term potentiation, learning and memory. A single nucleotide polymorphism (SNP), which produces a valine-to-methionine substitution at codon 66 (Val66Met) in BDNF leading to reduced activity-dependent secretion of BDNF. The BDNF Val66Met polymorphism has been associated with anxiety disorder, and abnormalities in hippocampal formation and cognitive function. Previous studies suggest that both food restriction and exercise elevate BDNF levels in the hippocampus. Here, we investigated whether food restriction and/or exercise during adolescence would rescue the behavioral deficits in BDNF-Val66Met knock-in mice. Four experimental groups of male and female pubertal BDNF-Val66Met knock-in mice and their wild-type littermates were evaluated: CON (singly housed mice with no running wheel experience or food restriction), and three experimental groups: EX (housed with a wheel from P36-44), FR (food restricted from P41-44), and FR-plus-EX (housed with a running wheel from P36-44 and food restriction from P41-44). We assessed anxiety-related levels of these animals after recovery from food restriction by elevated plus maze. Spatial and object recognition memory and social preference and recognition of the animals were also tested after recovery from food restriction. Our preliminary data suggest that, during early adulthood, male BDNFMet/Met mice display increased anxiety-like level and show impaired spatial, object recognition memory, and social recognition ability. EX, FR, and FR-plus-EX during adolescence have no effect on anxiety-like level in BDNFMet/Met mice. However, EX, FR, and FR-plus-EX show differential effects but mostly rescue the spatial, object recognition memory, and social recognition deficits of BDNFMet/Met mice to levels of BDNFVal/Val controls. On the other hand, female BDNFMet/Met mice display normal spatial memory and social recognition ability, but increased anxiety-like level and impaired object recognition memory. EX, FR, and FR-plus-EX can rescue the object recognition memory deficits in BDNFMet/Met female mice. This study highlights sex differences in the effects of BDNF Val66Met polymorphism on cognitive functions, while anxiety-like behavior is similar across the sexes. This study also provides evidence for the effects of food restriction and/or exercise during adolescence on rescuing the behavioral deficits in BDNFMet/Met mice.