Age Associated Downregulation of Glutamate/GABA Transporters Expression in Rostral Ventral Lateral Medulla (RVLM)

Abstract

Physiological function is altered with advancing age, including changes in sympathetic nervous system regulation. Studies focused on Glutamate/GABA ionotropic receptors using pharmacological agonists and antagonists in the rostral ventral lateral medulla (RVLM) indicates changes in medullary mechanisms regulating sympathetic nerve discharge (SND) in aged Fisher 344 rats. Identifying molecular mechanisms involved in this alteration is necessary to understand the regulation of central sympathetic neural circuits. Based on this rationale, we hypothesized that aging alters the basal regulation of RVLM Glutamate/GABA system‐associated genes. To test this hypothesis, the RVLM containing area was micro‐punched from young, middle‐aged and aged Fisher 344 rats. RNA level expression changes in RVLM GABA/Glutamate system‐associated genes were analyzed using RT2 profiler array and Taqman® real‐time PCR. Genes that showed >2fold differences in expression were analyzed at protein level by using immunoblot analysis. Downregulation of RVLM glutamate (Slc1a6) and GABA (Slc6a13) transporter genes was observed in aged compared with young rats at the RNA level, with a similar trend at the protein level. Slc1a6 and Slc6a13 transporters are known to modulate the amount of Glutamate/GABA in synaptic cleft and extra synaptic space. Down regulation of these transporters suggests there may be an altered Glutamergic/GABAergic balance in the aged RVLM.Support or Funding InformationSupported by NIH AG‐041948.