The role of inhibitory neurotransmitters on macrophage function during neuroinflammation

Abstract

GABA and glycine are the main inhibitory neurotransmitters of the mammalian central nervous system (CNS). Moreover, they participate in the communication between the CNS and the immune system. GABA and glycine levels are altered in the CSF and plasma of EAE rats and MS patients indicating a possible role of these inhibitory neurotransmitters in the disease pathogenesis. Therefore, the aim of this study was to determine the modulatory effect of GABA and glycine on macrophage functions playing a role in neuroinflammation. Macrophages clearly expressed the GABA-R, Gly-R/gephyrin and GLYT1&2. Glycine dose-dependently decreased the NO production and myelin phagoyctosis of peritoneal rat macrophages in a receptor-independent manner. Evidence provided by using transporter blockers and L-serine suggests that glycine could mediate its effect via an intracellular pathway. In contrast, GABA blunted increases in NO production, myelin phagocytosis and ROS production and these effects were shown to