alexa Abstract | Selective loss of Purkinje cells in non-phosphorylated form of neurofilament heavy chain-defined compartments in the cerebellum of tottering mice

Current Neurobiology
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Tottering mouse is an ataxic mutant that carries a mutation in a gene encoding for the ?1A subunit of P/Q-type Ca2+ channel (Cav2.1), and exhibits Purkinje cells loss with the zebrin II immunonegative population in the anterior vermis and the zebrin II immunopositive population in the caudal vermis. This study aimed to clarify relationship between patterns of Purkinje cell loss in the tottering cerebellum with expression of non-phosphorylated forms of the neurofilament heavy chain (NFH), which was recognized by ani-SMI-32. SMI-32 immunostaining has appeared in particular subsets of Purkinje cells, which were organized into parasagittal stripes throughout the cerebellar cortex of control mice. In tottering mice, SMI-32 stripes in the vermis disappeared from the a selective loss of SMI-32 immunopositive Purkinje cells. When the phosphorylation state of NFH was examined immunohistochemically using anti-SMI-31, which recognizes phosphorylation epitopes of NFH, no Purkinje cell soma were labeled in either tottering or control mice. In addition, while a number of Purkinje cell axonal torpedoes were observed in tottering mice but not in control mice, all torpedoes were stained with both anti-SMI-32 and anti-SMI-31, revealing the presence of both phosphorylated and non-phosphoryalted forms of NFH in the torpedoes. These results predict that the non-phosphorylated form of NFH expressing cerebellar Purkinje cells is susceptible to the Cav2.1 gene defect to degenerate those neurons. This may result in the characteristic parasagittal pattern of Purkinje cell loss in tottering mice.

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Author(s): Kazuhiko Sawada and Yoshihiro Fukui


Ca2+ channelopathy, Compartmentation, Degeneration, Torpedoes, Ataxia

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