Effect of a polymorphic allele in the BDNF gene on the neuronal structure

AGUSTÍN ANASTASÍA GONZALEZ; GUADALUPE GAZAL

La Falda

Congreso; Reunion de la Sociedad de Biología de Cordoba; 2017

Sociedad de Biología de Cordoba

There is a single nucleotide polymorphism (SNP) in the BDNF gene (rs6265) which is associated with increased susceptibility to develop neuropsychiatric disorders in human carriers. This SNP is present in approximately 25% of the world population, with a distribution of 20% in heterozygosity and 5% in homozygosity. This SNP induces a substitution of a valine for a methionine within the prodomain of BDNF, an abundant peptide in the central nervous system. The prodomain of BDNF variant Met elicits morphological changes in immature and mature neurons in culture, but it remains yet unknown the effects of both prodomains Val and Met together as a model for the expression in the heterozygote carriers. To begin to answer this question we studied the effects of polymorphic variants simultaneously on hippocampal neurons in culture at different DIVs. We measured diverse parameters in the establishment of polarity, in the development of dendrites and axons, and in the establishment of synapses of these neurons in the presence of both peptides. These experiments will allow unmasking whether there is competition between the two variants of the BDNF prodomain, and the consequences that can have on neuronal development. Additionally, the results obtained could provide a molecular explanation for the increased incidence of neuropsychiatric diseases in the human carriers of the rs6265 SNP.