Purkinje cells in olivopontocerebellar atrophy and granule cell-type cerebellar degeneration: an immunohistochemical study

We carried out immunohistochemical studies on cerebellar Purkinje cells in sporadic olivopontocerebellar atrophy (OPCA) and in granule cell-type cerebellar degeneration (gc-CD). The cell bodies, axons and dendrites including spiny branchlets and dendritic spines of normal Purkinje cells were intensely stained by the antibody against P(400) glycoprotein/inositol 1,4,5-trisphosphate receptor protein (P(400)/IP(3)R). The staining pattern of OPCA Purkinje cells was heterogeneous: some were negative, while others were stained with various intensities. Although a small number of P(400)/P(3)R-positive Purkinje cells in OPCA were similar to the normal ones, the immunoreaction products in OPCA Purkinje cells disappeared from the dendritic spines and spiny branchlets toward the cell bodies. Some of OPCA Purkinje cells were stained by the antibodies to phosphorylated neurofilament proteins (pNFP), synaptophysin and alpha B-crystallin. Normal Purkinje cells did not express pNFP, synaptophysin or alpha B-crystallin. By contrast, the staining pattern of the Purkinje cells of gc-CD case was uniform: almost all the Purkinje cells expressed P(400)/IP(3)R in cell bodies, axons and dendrites, but not in the dendritic spines and spiny branchlets. Our data suggest that the function of OPCA Purkinje cells is impaired from the peripheral dendrites toward the cell bodies, and that the presence of aberrant phosphorylation of neurofilament proteins, synaptophysin and alpha B-crystallin may be related to the degeneration of Purkinje cells in OPCA. In the gc-CD, our results suggest that the lack of P(400)/P(3)R immunoreactivity in dendritic spines and spiny branchlets of the Purkinje cells is related to the loss of inputs from the granule cells as well as the result of maldevelopment of the Purkinje cells.