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

机译:小鼠大脑中胰岛素受体蛋白的性别和区域特异性表达:轻度抑制氧化磷酸化的作用

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摘要

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.
机译:胰岛素受体(IR)和氧化代谢的抑制已被建议参与神经退行性疾病的病理生理级联。这项研究的目的是调查轻度低氧发作后小鼠大脑中胰岛素受体蛋白表达的性别和区域特异性。由未经处理的雄性和雌性小鼠以及体内经20mg / kg体重预处理的动物制备组织。组织制备前1小时,加入3-硝基丙酸(3-np;琥珀酸脱氢酶抑制剂)。雌性在发情期和发情期中,对照动物中的IR表达相似,但在发情期中IR表达降低。预处理后,雄性海马中IR蛋白表达下降,但在其他地区和雌性中IR蛋白表达仍然相同。总而言之,IR蛋白的表达在男性和女性中是区域性的,性别相关,并且在女性的发情周期阶段受到调节。与预期相反,在雌性的任何区域中对氧化磷酸化的轻度抑制均未进行修饰,而仅在雄性的海马中发生了改变。但是,后一种效应值得进一步研究,涉及参与影响海马的病理生理级联反应,例如阿尔茨海默氏病。

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