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Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice
Biology of Sex Differences ( IF 7.9 ) Pub Date : 2020-11-16 , DOI: 10.1186/s13293-020-00337-0
Dany Arsenault 1, 2, 3 , Cyntia Tremblay 2 , Vincent Emond 2 , Frédéric Calon 1, 2
Affiliation  

While the higher prevalence of Alzheimer’s disease (AD) in women is clear, studies suggest that biological sex may also influence AD pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms. First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst afterhyperpolarization (AHP), and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas the paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar. In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.

中文翻译:

老年杂合 3xTg-AD 小鼠内嗅皮层神经元生理的性别依赖性改变

虽然女性阿尔茨海默病 (AD) 的患病率较高是显而易见的,但研究表明,生理性别也可能影响 AD 的发病机制。然而,这些差异背后的机制尚不清楚。为了在大脑细胞水平上研究两性之间的生理差异,我们在 20 个月大的两性 3xTg-AD 杂合小鼠中研究了内嗅皮层神经元的内在和突触特性。选择这个大脑区域是因为它与 AD 症状的早期关联。首先,我们发现雄性和雌性非转基因小鼠之间的生理差异,提供了老年雌性轴突改变的间接证据。其次,我们观察到发射活动的转基因依赖性升高,爆发后超极化(AHP),和自发兴奋性突触后电流 (EPSC) 活动,不受性别影响。第三,被动特性和超极化激活电流 (Ih) 仅在雌性小鼠中被转基因表达改变,而诱发 EPSC 的配对脉冲比 (PPR) 仅在雄性中改变。第四,性别和转基因表达都与动作电位特性的变化有关。与之前的工作一致,在 3xTg-AD 雌性中检测到更高水平的 Aβ 神经病理学,而 tau 沉积相似。总之,我们的结果支持衰老和 AD 神经病理学差异改变男性和女性内嗅皮层神经元生理学的观点。被动特性和超极化激活电流 (Ih) 仅在雌性小鼠中被转基因表达改变,而诱发的 EPSC 的配对脉冲比 (PPR) 仅在雄性中改变。第四,性别和转基因表达都与动作电位特性的变化有关。与之前的工作一致,在 3xTg-AD 雌性中检测到更高水平的 Aβ 神经病理学,而 tau 沉积相似。总之,我们的结果支持衰老和 AD 神经病理学差异改变男性和女性内嗅皮层神经元生理学的观点。被动特性和超极化激活电流 (Ih) 仅在雌性小鼠中被转基因表达改变,而诱发的 EPSC 的配对脉冲比 (PPR) 仅在雄性中改变。第四,性别和转基因表达都与动作电位特性的变化有关。与之前的工作一致,在 3xTg-AD 雌性中检测到更高水平的 Aβ 神经病理学,而 tau 沉积相似。总之,我们的结果支持衰老和 AD 神经病理学差异改变男性和女性内嗅皮层神经元生理学的观点。在 3xTg-AD 雌性中检测到更高水平的 Aβ 神经病理学,而 tau 沉积相似。总之,我们的结果支持衰老和 AD 神经病理学差异改变男性和女性内嗅皮层神经元生理学的观点。在 3xTg-AD 雌性中检测到更高水平的 Aβ 神经病理学,而 tau 沉积相似。总之,我们的结果支持衰老和 AD 神经病理学差异改变男性和女性内嗅皮层神经元生理学的观点。
更新日期:2020-11-16
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