DOI: 10.1523/jneurosci.0808-04.2004. Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy

Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy

10.1523/jneurosci.0808-04.2004

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Transgenic models of neurodegenerative disease have proved uniquely powerful for delineating pathways of neuronal dysfunction and cell death. We have developed a transgenic model of the polyglutamine disease spinal and bulbar muscular atrophy (SBMA), an adult-onset, slowly progressive motor neuron disease caused by polyglutamine expansion in the androgen receptor (AR). Mice bearing a human AR with 112 glutamines reproduce many aspects of SBMA, including slowly progressive, gender-specific motor deficits, and neuronal intranuclear inclusions. Despite substantial motor deficits in male AR112Q mice, no motor neuron loss was observed, indicating that neuronal dysfunction, rather than neuronal death, is central to disease. Moreover, reduced levels of unphosphorylated neurofilament heavy chain (NF-H) were observed in motor neurons, suggesting a role for NF-H in SBMA neuronal dysfunction. The elimination of androgens by surgical castration of severely affected, aged 112Q male mice partially restored motor function as well as NF-H levels. These data suggest that hormone-based therapies designed to treat SBMA patients, even with advanced disease, are likely to be effective.

Bibliography

Chevalier-Larsen, E. S., OâBrien, C. J., Wang, H., Jenkins, S. C., Holder, L., Lieberman, A. P., & Merry, D. E. (2004). Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy. The Journal of Neuroscience, 24(20), 4778â4786.

Authors 7

Erica S. Chevalier-Larsen (first)
Christopher J. O'Brien (additional)
Huiyi Wang (additional)
Shannon C. Jenkins (additional)
Latia Holder (additional)
Andrew P. Lieberman (additional)
Diane E. Merry (additional)

References 44 Referenced 178

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Dates

Type	When
Created	21 years, 3 months ago (May 19, 2004, 3:48 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 12:09 p.m.)
Indexed	1 month, 4 weeks ago (June 30, 2025, 10:29 a.m.)
Issued	21 years, 3 months ago (May 19, 2004)
Published	21 years, 3 months ago (May 19, 2004)
Published Online	21 years, 3 months ago (May 19, 2004)
Published Print	21 years, 3 months ago (May 19, 2004)

Funders 0

None

BibTeX

@article{Chevalier_Larsen_2004, title={Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy}, volume={24}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.0808-04.2004}, DOI={10.1523/jneurosci.0808-04.2004}, number={20}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Chevalier-Larsen, Erica S. and O’Brien, Christopher J. and Wang, Huiyi and Jenkins, Shannon C. and Holder, Latia and Lieberman, Andrew P. and Merry, Diane E.}, year={2004}, month=may, pages={4778–4786} }

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