Journal
JOURNAL OF NEUROSCIENCE
Volume 35, Issue 46, Pages 15326-15338Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2724-15.2015
Keywords
neurodegeneration; neurodevelopment; oxidative stress; parvalbumin interneurons; selenium; sex differences
Categories
Funding
- National Institutes of Health [G12 MD007601, R01 DK47320]
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Selenium (Se) is essential for both brain development and male fertility. Male mice lacking two key genes involved in Se metabolism (Scly(-/-) Sepp1(-/-) mice), selenoprotein P (Sepp1) and Sec lyase (Scly), develop severe neurological dysfunction, neurodegeneration, and audiogenic seizures that manifest beginning in early adulthood. We demonstrate that prepubescent castration of Scly(-/-) Sepp1(-/-) mice prevents behavioral deficits, attenuates neurodegeneration, rescues maturation of GABAergic inhibition, and increases brain selenoprotein levels. Moreover, castration also yields similar neuroprotective benefits to Sepp1(-/-) and wild-type mice challenged with Se-deficient diets. Our data show that, under Se-compromised conditions, the brain and testes compete for Se utilization, with concomitant effects on neurodevelopment and neurodegeneration.
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