Synaptic prion protein immuno-reactivity in the rodent cerebellum

The cellular prion protein PrPc is a neurolemmal glycoprotein essential far the development of the transmissible spongiform encephalapathies. In these neurodegenerative diseases, host PrPc is converted to infectious protease- resistant isoforms PrPres or prions. Prions provoque predictable and distin ctive patterns of PrPres accumulation and neurodegeneration depending on th e prion strain and on regional cell-specific properties modulating PrPc aff inity for infectious PrPres in the host brain. Synaptolysis and synaptic ac cumulation of PrPres during PrP-related diseases suggests that the synapses could be primary sites able to propagate PrPres and neurodegeneration in t he central nervous system. Ln the rodent cerebellum, the present Light and electron microscopic immuno-cytochemical analysis shows that distinct types of synapses display differential expression of PrPc, suggesting that synap se-specific parameters could influence neuro-invasion and neurodegeneration following cerebral infection by prions. Although the physiological functio ns of PrPc remain unknown, the concentration of PrPc almost exclusively at the Purkinje cell synapses in the cerebellum suggests its critical involvem ent in the synaptic relationships between cerebellar neurons in agreement w ith their known vulnerability to PrP deficiencies. (C) 2000 Wiley-Liss, Inc .