A hyperglycinergic rat model for the pathogenesis of schizophrenia: preliminary findings.
There is evidence of high glycine concentrations in the brains and periphery of schizophrenics. In the forebrain, glycine plays a major role as a co-agonist with glutamate at the excitatory N-methyl-D-aspartate (NMDA) receptors. This activity of glycine is involved in the normal functioning of the brain in adulthood and during neurodevelopment, and it may also cause neurotoxicity and brain abnormalities when its concentrations are high. To test the hypothesis that the high glycine concentrations observed in schizophrenics play an etiologic role in schizophrenia, an animal model was tested where rats were made hyperglycinic from life in utero to adulthood. The hyperglycinic rats showed abnormalities in sensory gating mechanisms, enlarged cerebral ventricles and diminished hippocampal dimensions. All of these abnormalities closely parallel observations reported in patients with schizophrenic psychoses. These results from a rat model suggest an etiologic role for high glycine concentration in the behavior and brain abnormalities of schizophrenic patients.
Psychiatry Research-MEB, University of Iowa College of Medicine, Iowa City 52242-1000, USA. rafiq-waziri@uiowa.edu
R
R
Waziri
S
S
Baruah
D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry; D002552:Cerebral Ventricles / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005998:Glycine / Q000032:analysis* / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000209:etiology*; D012678:Sensation Disorders / Q000150:complications
D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine