Mechanisms of apoptosis during reovirus infection.

Reovirus infection has proven to be an excellent experimental system for studying mechanisms of virus-induced pathogenesis. Reoviruses induce apoptosis in a wide variety of cultured cells in vitro and in target tissues in vivo, including the heart and central nervous system. In vivo, viral infection, tissue injury, and apoptosis colocalize, suggesting that apoptosis is a critical mechanism by which disease is triggered in the host. This review examines the mechanisms of reovirus-induced apoptosis and investigates the possibility that inhibition of apoptosis may provide a novel strategy for limiting virus-induced tissue damage following infection.

Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells.

The role of protein kinase C and intracellular Ca(2+) on amphetamine-mediated dopamine release through the norepinephrine plasmalemmal transporter in undifferentiated PC12 cells was investigated. The selective protein kinase C inhibitor chelerythrine completely inhibited endogenous dopamine release elicited by 1 microM amphetamine. Direct activation of protein kinase C increased dopamine release in a Ca(2+)-insensitive, imipramine-sensitive manner and the release was not additive with amphetamine. Exocytosis was not involved since these events were not altered by either deletion of extracellular Ca(2+) or reserpine pretreatment. Down-regulation of protein kinase C activity by long-term phorbol ester treatment resulted in a dramatic decrease in amphetamine-mediated dopamine release with no apparent effect on [(3)H]dopamine uptake. To more completely examine a role for Ca(2+), intracellular Ca(2+) was chelated in the cells. Depletion of intracellular Ca(2+) considerably decreased dopamine release in response to 1 microM amphetamine compared with vehicle-treated cells, but had no effect on the [(3)H]dopamine uptake. Thus, our results suggest that amphetamine-mediated dopamine release through the plasmalemmal norepinephrine transporter is highly dependent on protein kinase C activity and intracellular but not extracellular Ca(2+). Furthermore, protein kinase C and intracellular Ca(2+) appear to regulate [(3)H]dopamine inward transport and amphetamine-mediated outward transport of dopamine independently in PC12 cells.

Metabotropic glutamate receptor mRNA expression in the schizophrenic thalamus.

BACKGROUND: The central role that the thalamus plays in information processing and sensory integration suggests that its dysfunction may be a factor in the pathophysiology of schizophrenia. Glutamate is a key neurotransmitter in thalamic function, and although all aspects of thalamic glutamate neurotransmission have not been elucidated, transcripts encoding members of each family of the glutamate receptors have been identified in the thalamus. Recently, activation of group II metabotropic glutamate receptors (mGluRs) was demonstrated in rats to ameliorate the behavioral effects associated with exposure to phencyclidine, an uncompetitive NMDA receptor antagonist that can induce psychotic symptoms, suggesting the possibility of mGluR abnormalities in schizophrenia. We investigated whether expression of thalamic mGluR mRNA is altered in this illness. METHODS: We examined the expression of the transcripts encoding the mGluR1, 2, 3, 4, 5, 7, and 8 receptors in postmortem thalamic tissue samples from elderly schizophrenic and control subjects, using in situ hybridization. We identified six thalamic nuclei in each section (anterior, dorsomedial, lateral dorsal, central medial, reticular, and nuclei of the ventral tier). RESULTS: There were no differences between elderly schizophrenic and control subjects in the expression of mGluR1, 2, 3, 4, 5, 7, or 8 transcript levels in any of these six thalamic nuclei. CONCLUSIONS: mGluR mRNA expression is not abnormal in the thalamus of patients with schizophrenia. The modulatory roles proposed for mGluRs, and the potentially important relationship between mGluRs and NMDA receptors, suggest that mGluRs may be involved in the pathophysiology of schizophrenia, but this is not detectable at this level of gene expression.