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Journal Article
Research Support, Non-U.S. Gov't
Cerebellar Purkinje cells die by apoptosis in the shaker mutant rat.
Brain Research 2017 Februrary 16
Cerebellar Purkinje cells (PCs) die in humans leading to a variety of diseases including ataxia and essential tremor. The etiology underlying PC death is poorly understood. Shaker mutant rat is a unique animal model of progressive PC degeneration that is compartmentalized and of adult-onset. In shaker mutant rats, hereditary degeneration of at risk PCs occurs between 7 and 14 postnatal weeks of age as a natural phenotypic expression of the shaker mutation and at earlier or later ages depending upon experimental conditions in restricted anterior (ADC) and posterior (PDC) vermal degeneration compartments. Secure PCs in a flocculonodular survival compartment (FNSC) always survive. In this study, we investigated DNA fragmentation and active caspase-3 expression characteristic of apoptosis using immunofluorescence and fluorescence microscopy. We also sought to confirm the occurrence of apoptosis in at risk PCs using transmission electron microscope. Purkinje neurons were the only cerebellar cells labeled for TUNEL and immunoreactive to active caspase-3 in the shaker mutant. Active caspase-3 expression observed was spatially and temporally congruous with the pattern of calbindin immunolabeling of degenerating PCs that is characterized by dendritic atrophy, shrinkage of PC cell bodies and the appearance of PC axonal torpedoes. DNA fragmentation, detected by TUNEL, as well as ultrastructural morphological changes characteristic for apoptosis, provided additional evidence for the occurrence of apoptosis in at risk PCs.
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