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Cerebellar Purkinje cell death in the leaner mouse is partially dependent on caspase 3 activation, a possible role for mitochondrial or autophagic mediated cell death
Author(s) -
FrankCan Tamy,
Abbott Louise C
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a870-a
Subject(s) - cerebellum , purkinje cell , programmed cell death , microbiology and biotechnology , autophagy , biology , caspase , chemistry , neuroscience , apoptosis , biochemistry
The leaner mouse carries an autosomal recessive mutation in the pore forming subunit (α1A) of P/Q‐type voltage‐gated Ca 2+ channels. This mutation results in decreased P/Q‐type Ca 2+ current and altered Ca 2+ homeostasis. P/Q‐type channels are highly expressed in the cerebellum. One consequence of the leaner mutation is an abnormal loss of cerebellar granule cells and Purkinje cells during postnatal development. While cerebellar granule cell death has been characterized as an typical apoptotic process, the mechanism of leaner cerebellar Purkinje cell death remains unclear. Inhibition of caspase 3 in cerebellar organotypic cultures significantly rescued leaner Purkinje cells, but did not completely restore wild type numbers of Purkinje cells. MitoTracker Red labeling in acute cerebellar slices indicated a significant loss of mitochondrial membrane potential (ΔΨ m ). However, this loss of ΔΨ m did not correspond with cytosolic release of cytochrome C. Alternately, monodansylcadaverine, a marker for autophagic vacuoles, was significantly increased in leaner Purkinje cells, indicating possible induction of autophagic cell death. These findings suggest that caspase 3 is potentially activated by multiple cell death signaling pathways and that at least some leaner Purkinje cell death occurs independent of caspase 3 activation. Support in part: NIH P30EF09106 to LCA.