Does acute heat stress differentially-modulate expression of ionotropic neurotransmitter receptors in the RVLM of young and aged F344 rats?

Abstract

The rostral ventral lateral medulla (RVLM) is a brainstem area that plays a role in regulating numerous physiological systems, especially their responsiveness to acute stress. Aging affects the responsiveness of RVLM neural circuits to acute stress. Based on the relationship between ionotropic neurotransmitter receptors in the RVLM and the physiological functions mediated via activation of these receptors, we hypothesized that in response to acute heat stress the expression of ionotropic neurotransmitter receptors in the RVLM of aged rats would be characterized by upregulation of inhibitory subunits and downregulation of excitatory subunits. The goal of the present study was to determine the effect of acute heating on the gene expression profile of RVLM inhibitory (GABAA and Glycine) and excitatory (NMDA and AMPA) ionotropic neurotransmitter receptor subunits in young and aged F344 rats. RVLM tissue punches from young and aged F344 rats were analyzed using TaqMan qPCR and immunoblotting. When compared to age-matched controls, heat stress increased the gene expression of RVLM inhibitory receptor subunits in aged (Gabra1, Gabra2, Gabra5, Glra1) and young (Gabra1) F344 rats at mRNA level, with little change in the expression of RVLM excitatory receptor subunits. Significant age x heat interaction effects were observed with increased expression of Gabra2 and Gabrb1 inhibitory receptor subunits and decreased expression of Gria1 and Gria2 excitatory receptor subunits in the RVLM of aged F344 rats, with the most marked change observed with the Gabra2 subunit, which was validated by immunoblotting. These findings demonstrate that in response to acute heat stress there is enhanced expression of inhibitory ionotropic receptor subunits in aged compared to young rats, supporting the idea that advanced age may alter RVLM responsivity by affecting the molecular substrate of ionotropic receptors.