This project will address the hypothesis that persistent viral infection can alter neurotransmitter function to cause neurologic and psychiatric disease. A number of neurotransmitters have been defined and mapped to locations within the central nervous system. Abnormal levels of neurotransmitters have been found in several neurologic and psychiatric disorders and are suspected to occur in others. The mechanisms by which neurotransmitter concentrations are altered in these disorders and the etiologic agents responsible are largely unknown. Some viral infections have been found to effect neurologic and psychiatric dysfunction. Persistent virus infections can interfere with differentiated functions (elaboration of hormones and neurotransmitters) with or without histopathologic evidence of injury. Neurologic and psychiatric disorders, particularly those involving abnormal neurotransmitter synthesis or activity, may be linked to persistent virus infections. Lymphocytic choriomeningitis virus (LCMV) inoculated intracerebrally into newborn mice causes persistent neuronal infection with neurobehavioral dysfunction. Infection has been mapped to specific cells and regions within the cerebellum, dentate gyrus, hippocampus and neocortex. Coronal brain sections from mice persistently infected with LCMV will be studied for cell colocalization of LCMV and neurotransmitters found in these regions (cholecystokinin, y-aminobutyric acid and somatostatin) via immunohistochemistry and in situ hybridization. The concentration of these neurotransmitters and their mRNAs in infected and uninfected mice will be measured by brain region via radioimmunoassay, high pressure liquid chromatography and slot blot hybridization. This project is important in several aspects: (1) it may provide insight into the basis for neurologic and psychiatric dysfunction in known viral infections of the nervous system; (2) it may provide models of viral pathogenesis for neurotransmitter-associated diseases of unknown etiology; (3) it may lead to new strategies for management of viral infections of the nervous system.
| Carbone, K M; Moench, T R; Lipkin, W I (1991) Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats: location of viral genomic and messenger RNAs by in situ hybridization. J Neuropathol Exp Neurol 50:205-14 |
| de la Torre, J C; Carbone, K M; Lipkin, W I (1990) Molecular characterization of the Borna disease agent. Virology 179:853-6 |
| Lipkin, W I; Wilson, M C; Oldstone, M B (1990) Molecular insights into infections of the central nervous system. Res Publ Assoc Res Nerv Ment Dis 68:15-22 |
| Lipkin, W I; Carbone, K M; Wilson, M C et al. (1988) Neurotransmitter abnormalities in Borna disease. Brain Res 475:366-70 |
