Expression of Augmenter of Liver Regeneration (ALR) in female and Male Mouse Prosencephalon: A New Approach for the Comprehension of Gender-Related Brain Biology

L. Polimeno, L. Lorusso, G. Calamita, A. Tafaro, R. Tamma, M. D. Comite, A. Rizzi, L. Santacroce, D. Ribatti, V. Benagiano
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Abstract

Background: Augmenter of liver regeneration (ALR) is an antioxidant, antiapoptotic and mitochondrial-protective factor. Evidence exists that (i) ALR is variously expressed by many neurons in the central nervous system; (ii) ALR is differently expressed in female and male cells; (iii) neurodegenerative diseases triggered by dysregulation of cell normoxic conditions differently affect the 2 sexes. Aim: Aim of the present study was to analyze the ALR presence in the prosencephalon of female and male mice and evaluate whether differences in expression exist between the two genders. Methods: Harvested prosencephala were investigated by Western blotting and immunohistochemistry to assess ALR expression. Results: Western blotting revealed 2 ALR isoforms, ALR-21 and ALR-23, both more expressed in male prosencephalon. Immunohistochemistry revealed ALRimmunoreactive neurons diffusely distributed in the prosencephalon, but with a significantly higher number in male prosencephalon. Conclusion: The different ALR expression level in female and male mouse prosencephalon may represent a marker of sexual dimorphism. The higher ALR expression seen in male prosencephalic neurons suggests that ALR, an antioxidant factor, could parallel the antioxidant effect of female sex steroid hormones that are known to be more effective compared to the male sexual steroids in protecting against the oxidative stress. These data open new options to study the neurodegenerative diseases, particularly those showing gender differences in terms of epidemiology.
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肝再生增强因子(ALR)在雌雄小鼠前脑中的表达:一种理解性别脑生物学的新途径
背景:肝再生增强因子(Augmenter of liver regeneration, ALR)是一种抗氧化、抗凋亡和线粒体保护因子。有证据表明(i)中枢神经系统的许多神经元以不同的方式表达ALR;(ii) ALR在女性和男性细胞中的表达不同;(iii)由细胞正常状态失调引发的神经退行性疾病对两性的影响不同。目的:本研究的目的是分析雌性和雄性小鼠前脑中ALR的存在,并评估两性之间是否存在表达差异。方法:采用Western blotting和免疫组化方法检测采收的前脑ALR的表达。结果:Western blot结果显示2种ALR亚型ALR-21和ALR-23在男性前脑中表达较多。免疫组化显示,ALRimmunoreactive神经元弥漫性分布于前脑,但在雄性前脑中数量明显较多。结论:雌性和雄性小鼠前脑中ALR表达水平的差异可能是雌雄异形的标志。男性前脑神经元中较高的ALR表达表明,ALR作为一种抗氧化因子,可能与女性性类固醇激素的抗氧化作用相似,而女性性类固醇激素在抗氧化应激方面比男性性类固醇激素更有效。这些数据为研究神经退行性疾病,特别是那些在流行病学方面表现出性别差异的疾病开辟了新的选择。
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