Conserved role of brain-derived neurotrophic factor in Val66Met: target-selective reinforcement of GABAergic synapses

Brain-derived neurotrophic factor has been implicated in higher cognitive functions, and several neurological and psychiatric disorders. Recently, a variant brain-derived neurotrophic factor (BDNFMet), having a substitution referred to as Val66Met, was reported as a product of a bdnf allele with a common single nucleotide polymorphism. It has been reported that BDNFMet is impaired in its potential for activity-dependent release. We sparsely transfected cultured hippocampal neurons with BDNFMet or wild-type BDNFVal cDNAs and examined the amount of GABA-synthetic enzyme glutamic acid decarboxylase 65 (GAD65) in the adjacent region, probably in the GABAergic synapses. BDNFMet transfection increased the GAD65 level to the same extent as transfection with BDNFVal. Our findings suggest that the activity-independent secretion of brain-derived neurotrophic factor may be sufficient to induce inhibitory regulation.