GABAA receptor activation is involved in differentiation of embryonic hypothalamic neurons dependig of sex

MIR F.R; CAMBIASSO, M.J

Huerta Grande - Córdoba

Congreso; XXVII Congreso anual de la Sociedad Argentina de Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

GABA is the main inhibitory neurotransmitter in adult central nervous system; however during development it exerts trophic actions. The proposed mechanism for these effects is the activation of GABAA receptor mediated current, which elicit a depolarization and the opening of voltage-dependent calcium-channels. This calcium influx acts as a second messenger that modulates the activity of a variety of kinases. Some kinases, like CAMKII and p42/44 MAPK are involved in the GABA-induced neurite outgrowth of immature neurons. Previous results of our lab have demonstrated that hypothalamic neurons show sex differences in neurite differentiation in response to estradiol. To assess sex differences in GABA-mediated neuronal differentiation, male and female hypothalamic cultures were treated with a GABAA receptor agonist(muscimol 100µM) or antagonist (bicuculline 100µM) during 2 DIV. Neurite outgrowth, soma area, number of neurites and number of neurite ramifications were quantified by morphometric analysis in five independent cultures. Muscimol-treated cultures showed neurons with shorter axons than controls irrespective of sex (p< 0.01); whereas the media longitude of minor processes was larger in males than females (p< 0.001). The percentage of neurons in stage II is also increased in muscimol-treated male cultures (muscimol 42% vs.control 30%). The lack of immunofluorescence staining of Tau-1 protein in such neurons suggests they are arrested in differentiation.