Glycogen synthase kinase (GSK)-3beta levels and activity in a neurodevelopmental rat model of schizophrenia

We have previously reported reduced GSK-3beta protein levels and GSK-3 total (alpha + beta isoforms) activity in postmortem frontal cortex of schizophrenic patients. We now studied whether GSK-3beta is altered in the frontal cortex of rats with the neonatal excitotoxic hippocampal lesion used as a model of schizophrenia. Rats were infused with ibotenic acid (or artificial CSF in controls) bilaterally into the ventral hippocampus (VH) at postnatal day 7, then killed at postnatal day 35 (pre-puberty) or 56 (post-puberty). GSK-3beta protein levels were reduced in the frontal cortex of the lesioned rats as compared to sham animals; post-hoc comparisons revealed that the reduction was statistically significant at a pre-pubertal age. Total GSK-3 (alpha + beta) activity was not different between lesioned and sham rats at any age. These results demonstrate that reduced frontal cortical GSK-3beta levels may occur as a result of neonatal hippocampal damage and suggest that this animal model may be utilized to study the mechanism of GSK-3 reduction in schizophrenia, a disorder in which postmortem changes in GSK-3 were found.