Normal cellular prion protein, a necessary protagonist in fatal neurodegenerative prion diseases, was mapped in rodent cerebellum to establish its cellular and ultrastuctural localization. Existing morphological data about native prion protein distribution in brain tissues remain, indeed, contradictory and do not fit with biochemical and cell biological results. Using ultrastructural preembedding immunocytochemistry and a monoclonal anti-mouse prion protein antibody, this report shows that cellular prion protein is present in all cortico-cerebellar and deep nuclei neuronal cell types, as well as in all glial cell types. The heaviest expression appears on parallel fibres and astrocytic processes. The protein is exclusively located on the outer cell membrane and in Golgi and endosomal intracytoplasmic organelles, with no cytoplasmic or synaptic vesicle labelling. Most important, and in contrast with previous ultrastructural data, cellular prion protein is shown to be distributed on all portions of neurons, without any preferential synaptic targeting. The present morphological report shows, for the first time in vivo, that the cellular prion protein is present on the entire cell surface membrane of all neuronal and glial cell types of the rat cerebellum. This ubiquitous presence supports the notion that prion protein has a generalized cellular function in brain tissue rather than a specialized role restricted to synaptic transmission.
A new cell type is described in silver-impregnated sections of the rat cerebellar cortex, uniformly distributed through all the cerebellar folia. The soma is rather small, roughly pyriform, vertically oriented, and squeezed, in a sandwich-like manner, between the Purkinje cell somata. One or two thick dendrites arise from the upper pole of the cell body and course through the entire molecular layer, dividing into a few, slightly oblique, branches that can reach the pia mater. These dendrites are covered with irregularly distributed spines. Some more slender dendrites emerge from the lower part of the cell body, or from the proximal trunk of a molecular dendrite, and spread tortuously for a short distance in the upper granular layer. A thick initial segment emerges directly from the soma or from the proximal portion of a dendrite, the axon winding then horizontally through or just above the Purkinje cell layer. During this horizontal course it gives off vertically oriented beaded branches ascending through the major part of the molecular layer. These branches, rather closely spaced, occupy different parasagittal planes, separated by about 10 to 30 microns. This axonal arborisation can thus be compared with a candelabrum. The peculiar three-dimensional spread of the axonal collaterals suggests a functional relationship between these branches and the dendritic trunks of neighbouring Purkinje cells. A comparative analysis of the morphological differences between this candelabrum interneuron and the other corticocerebellar interneurons found in the vicinity of the ganglionic layer confirms the specificity of this new cell class.
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