DISTURBANCE OF THE CORTICAL CHOLINERGIC INNERVATION IN BORNA-DISEASE PRIOR TO ENCEPHALITIS

Rats experimentally infected with the highly neurotropic Borna disease virus (BDV) display a wide variety of dysfunction such as learning de ficiencies and behavioral abnormalities, Prior to the onset of encepha litis alterations of one of the major cortical neurotransmitters, acet ylcholine, were monitored immunohistochemically by light and electron microscopy of its synthesizing enzyme choline acetyltransferase (ChAT) , We found a progressing decrease in the number of ChAT-positive fiber s, starting with discrete changes at day 6 post infection (p.i.) and e nding with a nearly complete loss of cholinergic fibers, especially in the hippocampus and neocortex, suggesting a massive disturbance of th e cholinergic innervation by day 15 p.i.. The fiber pathways (e.g., fi mbria-fornix) connecting the basal forebrain with these target areas i n the cortex displayed axon spheroids which are often linked to axonal transport dysfunction. No evidence for significant cellular destructi on was seen in the brain, including the cells of origin of these axons in the basal forebrain, We conclude that the motor, mood, learning an d memory disabilities in BDV-infected rats are likely to result, in pa rt, from cortical cholinergic denervation. The present study gives new insights into the pathogenesis of neurological disease caused by a no ncytopathogenic virus.