The response to postnatal stress: Amino acids transporters and pkc activity

Abstract

During postnatal development, the central nervous system (CNS) is highly sensitive to effects of drugs, stressors and environment. In this study, we evaluated the effect of acute cold stress on g-aminobutyric acid (GABA) and L-serine (L-Ser) transporters in vitro, using the uptake of [3H]GABA and [3H]L-Ser by synaptosomes-enriched fractions isolated from rat cerebral cortex during postnatal development. We found that the maximal velocity (Vmax) L-Ser uptake after stress session was increased in almost all ages studied, except at postnatal-days (PD) 5, whereas the values of Km (uptake affinity) decreased in all ages from 5 to 21 PD compared with the control group. The highest values of Vmax and Km were obtained at PD7. At the same time, in GABA uptake, the Km decreased although Vmax increased in all ages considered after cold stress during development. Finally, we investigated the mechanism by which cells regulate the substrate affinity of L-serine and GABA transporters. We demonstrated a significantly increase in PKC activity to PD5 from PD21. Pretreatment with PKC inhibitor: staurosporine (SP) led to a restoration of control uptake in several postnatal-days suggesting a relationship between amino acids uptake and PKC activation. These findings suggest that a single exposure to postnatal cold stress at different periods after birth modifies both GABA and L-Ser transporters and the related increase in PKC activity could be intracellular events that participate in neuronal plasticity by early-life stress, which could be relevant to function of transporters in the adult rat brain.