Postnatal weight gain inhibition does not account for neurobehavioral consequences of neonatal Borna disease virus infection

Neonatal Borna disease virus (BDV) infection of the rat's brain produces neurodevelopmental damage similar to some pathological and clinical features of human developmental disorders, e.g., autism and schizophrenia. Since BDV-infected rats exhibited an inhibition of postnatal weight gain, the present study sought to evaluate a contribution of nutritional status to virus-induced neurodevelopmental injury. We compared neuroanatomical, neurochemical, and behavioral alterations following neonatal BDV infection and rearing in the oversized litters in Fischer344 rats on postnatal day (PND) 26. Despite a comparable weight gain inhibition, different patterns of brain pathology, alterations in brain monoamine systems, and behavioral deficits were observed in the BDV-infected rats compared to the malnourished rats. While no appreciable cell injury was noted in the brains of the malnourished rats, a significant loss of Purkinje cells (PC) and early signs of degeneration of the hippocampal dentate gyrus were found in the BDV-infected rats. Both neonatal BDV infection and postnatal malnourishment increased tissue concentrations of serotonin [5-hydroxytryptamine (5-HT)] in the hippocampus. In contrast, increased turnover of 5-HT in the cortex and hippocampus and elevated turnover of dopamine (DA) in the striatum were found in the malnourished rats only, suggesting that different pathogenic mechanisms might underlie monoamine disturbances in virus-infected and malnourished rats. The observed dissimilar neuroanatomical and neurochemical abnormalities might explain the different responses to novelty in the BDV-infected and malnourished rats. Compared to the control rats, the BDV-infected rats exhibited novelty-induced hyperactivity, while no differences in locomotion were noted between the control and malnourished rats. Taken together, the present data indicate that virus-associated inhibition of postnatal weight gain is unlikely to account for the major BDV-associated neurodevelopmental alterations that seem to be due to specific effects of neonatal BDV infection. (C) 2003 Elsevier Inc. All rights reserved.