Altered NMDA receptor expression and behavior following postnatal hypoxia: potential relevance to schizophrenia

Abstract

The present study investigated the effects of chronic, repeated hypoxia during a postnatal vulnerable period. Acoustic startle response in adult rats was measured along with NMDA receptor binding and mRNA expression of subunits at postnatal days (PND) 11 and 120. Rats at PND 120 exhibited a deficit in prepulse inhibition of acoustic startle response. In PND 11 rats, chronic hypoxia decreased NMDA receptor binding and increased transcript expression of NR1 subunit in frontal and temporal regions, nucleus accumbens and hippocampus, while NR2A subunit expression was downregulated in hippocampal subregions. At PND 120, gene expression of NR1 was still increased in hippocampal, frontal and temporal subregions as well as nucleus accumbens. A prepulse inhibition deficit points to schizophrenia-like behavior in adult (PND 120) rats. Compensatory upregulation of NR1 expression may occur due to NMDA receptor hypofunction. We discuss this animal model to further analyze effects of hypoxia as a factor of obstetric complications in the pathophysiology of schizophrenia.