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

Apoptosis constitutes a genetically determined process to eliminate superfl uous or damaged cells in tissues. Deficiencies in apoptosis regulation are involved in different pathologies including prion diseases. Some experiment al studies show that neuronal loss - one of the hallmarks of prion diseases may be accomplished by apoptosis. We evaluated twenty five mice infected e xperimentally with the Fujisaki strains of CJD and sacrified sequentially i n one week intervals. Apoptotic cells in various brain regions were detecte d by in situ end labelling (TUNEL) and electron microscopy in comparison wi th 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 t he 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. Compar ed to the extensive neuronal loss (30-50%), the number of apoptotic cells d etected by in situ end labelling seems to be very low, and the process of n euronal death become more intensive during the progression of the disease.