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Articles, Neurobiology of Disease

Sensory Neuropathy Attributable to Loss of Bcl-w

Stephanie L. Courchesne, Christoph Karch, Maria F. Pazyra-Murphy and Rosalind A. Segal
Journal of Neuroscience 2 February 2011, 31 (5) 1624-1634; DOI: https://doi.org/10.1523/JNEUROSCI.3347-10.2011
Stephanie L. Courchesne
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Christoph Karch
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Maria F. Pazyra-Murphy
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Rosalind A. Segal
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Abstract

Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small-diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w−/− mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w−/− sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w−/− mice as an animal model of small fiber sensory neuropathy and provide new insight regarding the role of Bcl-w and of mitochondria in preventing axonal degeneration.

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The Journal of Neuroscience: 31 (5)
Journal of Neuroscience
Vol. 31, Issue 5
2 Feb 2011
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Sensory Neuropathy Attributable to Loss of Bcl-w
Stephanie L. Courchesne, Christoph Karch, Maria F. Pazyra-Murphy, Rosalind A. Segal
Journal of Neuroscience 2 February 2011, 31 (5) 1624-1634; DOI: 10.1523/JNEUROSCI.3347-10.2011

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Sensory Neuropathy Attributable to Loss of Bcl-w
Stephanie L. Courchesne, Christoph Karch, Maria F. Pazyra-Murphy, Rosalind A. Segal
Journal of Neuroscience 2 February 2011, 31 (5) 1624-1634; DOI: 10.1523/JNEUROSCI.3347-10.2011
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