High dose glycine nutrition affects glial cell morphology in rat hippocampus and cerebellum

Enhancement of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission by glycine (Gly) administration may represent a novel pharmacological strategy in schizophrenia. Given the involvement of NMDA receptors in plasticity and excitatory processes, the present study explores effects of Gly on brain cell morphology. Adult rats were randomized to receive, for 2 wk, no dietary supplementation or supplementation with 0.8 or 3.2 g/kg per day Gly. Glial cell morphology was examined using antibodies to glial fibrillary acidic protein (GFAP) and to microglial complement receptor 3 (CR3). Cresyl violet was used for general cellular staining. No evidence of neuronal or microglial pathology was found. Although astrocyte proliferation was not evident in Gly-treated rats, GFAP-like immunoreactivity was dose-dependently increased in the hippocampus (p<0.01), whereas in cerebellum, a dose dependent decrease in density of astocytic fibres was demonstrated (p<0.01). These findings demonstrate for the first time that in vivo administration of high dose Gly may induce brain morphology changes.