Neuronal and glial alterations in the cerebellar cortex of maternally deprived rats: Gender differences and modulatory effects of two inhibitors of endocannabinoid inactivation

Abstract

Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. Accordingly, this experimental procedure has been proposed as an animal model of schizophrenia based on the neurodevelopmental hypothesis. We have recently reported that MD-induced sex-dependent alterations in the hippocampus of neonatal rats. In view of recent evidence for important implications of the cerebellum in neurodevelopmental psychiatric diseases, we have now addressed possible degenerative changes in the cerebellar cortex of neonatal Wistar rats of both genders. To evaluate the presence of degenerated nerve cells, we used Fluoro-Jade C staining and for the study of astrocytes, we employed glial fibrillary acidic protein. Further, we analyzed the modulatory actions of two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin, AA-5-HT, and the endocannabinoid reuptake inhibitor, OMDM-2 (daily subcutaneous injections during the postnatal period 7-12). The animals were sacrificed at postnatal Day 13. MD induced significant increases in the number of Fluoro-Jade C positive cells (indicative of degenerating neurons) and in the number of glial fibrillary acidic protein positive cells, only in males. The two cannabinoid compounds reversed or attenuated these effects. The present results provide new insights regarding the psychopathological implications of the cerebellum, the role of the endocannabinoid system in neural development, and the possible neurodevelopmental basis of gender differences in schizophrenia.