Consequences of early adverse life events on GABAergic

M M ODEON; A E SALATINO; GB ACOSTA

Trends in Comparative Biochemistry & Physiology

Research Trends (P) Ltd.

Lugar: Trivandrum - 695012, Kerala,; Año: 2011 vol. 15 p. 67 - 72

0972-4540

Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Several investigations have demonstrated its impact both on the activity of the hypothalamic-pituitary-adrenal axis (HPA) and the development of psychoemotional disorders later in adult life. The lifespan of the predominant inhibitory neurotransmitter in the central nervous system (CNS): ã-aminobutyric acid (GABA), is determined by its uptake into neurons and glia, through high-affinity Na+/Cl− dependent transporters (GATs). The aim of this research was to evaluate the effects of acute and chronic maternal separation (AMS and CMS) plus cold stress from frontal cortex (FC) and hippocampus (Hic) on the expression levels of GAT-1 using immunoblotting whose appearance correlates with the plasmatic corticosterone levels at different postnatal days (PD) from birth to adulthood. To explain these phenomena, we used Western blotting to evaluate the alterations in the expression of Hic and FC GABA transporter proteins. In response to AMS + cold stress in FC we found that a decrease expression of GAT-1 at PD13. On the contrary, in CMS + cold stress we have demonstrated an increase in the levels of the expression of GAT-1 both at PD57 and PD63. In Hic, AMS + cold stress increased the levels of GAT-1 expression both at PD7 and PD13. When we study CMS + cold stress we showed a decrease at PD57 and PD63 meanwhile an important increased at PD71 of hippocampal levels expression of GAT-1. With respect to the levels of corticosterone we found an increase in all age groups studied in AMS. Conversely, we have seen a decrease in corticosterone concentrations except at PD71 in CMS. In summary, low responsiveness of the early postnatal period to stress are involvements of GABAergic system, suggesting that GATs may contribute to the deregulations of neuronal excitability that accompany neurobiological consequences of early stress: schizophrenia, epilepsy, ischemia, anxiety and depression. Our results serve as a starting point elucidating the molecular mechanism of transporter regulation in GABA pathways during postnatal development.