Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice

Neurone damage and eventual loss may underlie the clinical signs of disease in the transmissible spongiform encephalopathies (TSEs). Although neurone death appears to be through apoptosis, the trigger for this form of cell de ath in the TSEs is not known. Using two different murine scrapie models, hi ppocampal pyramidal cells were studied through microinjection of fluorescen t dye, and synaptic integrity, using p38-immunoreactivity (p38-IR), both vi sualized using confocal laser scanning microscopy. Intradendritic distensio ns and dendritic spine loss were found to co-localize to areas of vacuolar and prion protein pathology in the hippocampus of mice infected with ME7 or 87 V scrapie. A significant reduction in p38-IR was found concomitantly in the hippocampus in ME7 scrapie mice. These results indicate that both pre- and post-synaptic sites are altered by scrapie infection; this would disru pt neuronal circuitry and may initiate apoptotic cell death, giving rise to the neurological disturbances manifested in clinical TSE cases.