■氧化应激相关认知功能下降的性别差异受性激素水平的影响。值得注意的是,氧化应激相关的神经元细胞死亡可以通过膜雄激素受体AR45通过睾酮信号传导加剧,AR45与质膜相关的脂筏内的G蛋白Gαq复合。这项研究的目的是阐明性别对与认知功能相关的脑区AR45和Gαq表达的影响,特别是海马亚区和内嗅皮层。此外,我们调查了慢性间歇性缺氧(CIH),具有性别特异性效应的氧化应激源,会调节这些脑区的AR45和Gαq表达。
■成年雄性和雌性Sprague-Dawley大鼠在睡眠期暴露于CIH或常氧(室内空气)14天。我们量化了不同认知相关脑区的AR45和Gαq蛋白表达[背侧海马CA1,CA3,齿状回(DG),和内嗅皮层(ETC)]通过蛋白质印迹。为了进行比较,还在海马-ETC回路[丘脑(TH)和纹状体(STR)]以外的脑区评估了AR45和Gαq蛋白表达。
■在海马CA1和DG中表达最高的AR45水平,而在海马外STR中观察到最低的表达。在海马相关的ETC中表达最高的Gαq水平,而在海马外TH中观察到最低的表达。与男性相比,女性在海马DG中表达更高水平的AR45,而无论评估的大脑区域如何,均未观察到Gαq表达的性别差异。此外,CIH对所检查的任何脑区的AR45或Gαq表达均无影响.CA1、DG中AR45表达与Gαq表达呈正相关,ETC,TH,和STR以性别依赖的方式。
■我们的发现揭示了海马-ETC回路中AR45和Gαq蛋白表达的富集,在认知衰退期间容易受到氧化应激和神经变性的影响。尽管如此,CIH不调节AR45或Gαq的表达。重要的是,AR45在不同脑区的表达及其与Gαq表达的相关性存在性别差异,这可能是认知和运动功能与衰老相关下降的性别差异的基础。
UNASSIGNED: Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. Notably, oxidative stress-associated neuronal cell death can be exacerbated through testosterone signaling via membrane androgen receptor AR45, which is complexed with G protein Gαq within plasma membrane-associated lipid rafts. The objective of this study was to elucidate the impact of sex on the expression of AR45 and Gαq in brain regions associated with cognitive function, specifically hippocampus subregions and entorhinal cortex. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and Gαq expression in these brain regions.
UNASSIGNED: Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia (room air) during their sleep phase for 14 days. We quantified AR45 and Gαq protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, dentate gyrus (DG), and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and Gαq protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)].
UNASSIGNED: The highest AR45 levels were expressed in the hippocampal CA1 and DG while the lowest expression was observed in the extrahippocampal STR. The highest Gαq levels were expressed in the hippocampal-associated ETC while the lowest expression was observed in the extrahippocampal TH. Females expressed higher levels of AR45 in the hippocampal DG compared to males, while no sex differences in Gαq expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or Gαq expression in any of the brain regions examined. AR45 expression was positively correlated with Gαq expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner.
UNASSIGNED: Our findings reveal enrichment of AR45 and Gαq protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Nonetheless, CIH does not modulate the expression of AR45 or Gαq. Importantly, there are sex differences in AR45 expression and its association with Gαq expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.