Gender- and region-specific expression of insulin receptor protein in mouse brain: effect of mild inhibition of oxidative phosphorylation

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Abstract
Insulin receptors (IR) and inhibition of oxidative metabolism have been suggested to partake in the pathophysiological cascade of neurodegenerative disorders. The goal of this study was to investigate gender- and region-specificity of insulin receptor protein expression in mouse brain subsequent to a mild hypoxic episode. Tissue was prepared from untreated male and female mice and animals pretreated in vivo with 20 mg/kg body weight i.p. 3-nitroproprionic acid (3-np; an inhibitor of succinic dehydrogenase) 1 hr prior to tissue preparation. IR expression in control animals was alike in males and females during proestrus and estrus but reduced during diestrus. On pretreatment, IR protein expression decrease in hippocampus in males but remained alike in other regions and females. In summary, IR protein expression is regionally different in males and females, gender-dependent, and modulated during the stages of the estrus cycle in females. Contrary to expectations it is not modified on mild inhibition of oxidative phosphorylation in any region in females and altered in hippocampus solely in males. The latter effect, however, warrants further scrutiny concerning participation in pathophysiological cascades affecting the hippocampus such as in Alzheimer’s disease.

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