Apoptosis in relation to neuronal loss in experimental Creutzfeldt-Jakob disease in mice.

Apoptosis constitutes a genetically determined process to eliminate superfluous or damaged cells in tissues. Deficiencies in apoptosis regulation are involved in different pathologies including prion diseases. Some experimental studies show that neuronal loss--one of the hallmarks of prion diseases may be accomplished by apoptosis. We evaluated twenty five mice infected experimentally with the Fujisaki strains of CJD and sacrified sequentially in one week intervals. Apoptotic cells in various brain regions were detected by in situ end labelling (TUNEL) and electron microscopy in comparison with neuronal cell loss. The number of labelled cells per brain was very low--from a few labelled cells 6 weeks after inoculation to a maximum of 14 in the terminal stage. The number of neurones counted in 8 selected areas were considerably lower in terminally sick animals (20 and 21 week of incubation period) than in control mice. The mean value of loss of neuronal cells was 32%. The greatest loss (55%) of neurones was noted in the septal nuclei of the paraterminal body and the least lost (16%) in the hypothalamus. Compared to the extensive neuronal loss (30-50%), the number of apoptotic cells detected by in situ end labelling seems to be very low, and the process of neuronal death become more intensive during the progression of the disease.