We showed previously in a mouse model of vascular cognitive impairment and dementia involving chronic cerebral hypoperfusion (CCH) that repetitive hypoxic conditioning (RHC) of both parents results in the epigenetic, intergenerational transmission of resilience to recognition memory loss in adult progeny, as assessed by the novel object recognition test. The present study was undertaken in the same model to determine whether RHC treatment of one or both parents is required to confer dementia resilience intergenerationally. We found inherited resilience to 3 months of CCH in males is maternally mediated (p = .006). Statistically, we observed a strong trend for the paternal germline to contribute as well (p = .052). We also found that, in contrast to what is widely observed in males, females display intact recognition memory (p = .001) after 3 months of CCH, revealing a heretofore unidentified sexual dimorphism with respect to cognitive impact during disease progression. Overall, results of our study strongly implicate epigenetic changes in maternal germ cells, induced by our repetitive systemic hypoxic stimulus, contributing to a modified differentiation program capable of establishing a dementia-resilient phenotype in adult male first-generation progeny. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

中文翻译：

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交配前母体重复缺氧赋予雄性后代记忆障碍的表观遗传弹性。

我们之前在涉及慢性脑灌注不足 (CCH) 的血管性认知障碍和痴呆小鼠模型中表明，父母双方的重复低氧调节 (RHC) 导致成年后代识别记忆丧失的表观遗传、代际传递弹性，如通过评估新物体识别测试。本研究是在同一模型中进行的，以确定是否需要对父母一方或双方进行 RHC 治疗，以在代际间赋予痴呆症复原力。我们发现男性对 3 个月 CCH 的遗传恢复力是母性介导的 (p = .006)。从统计学上讲，我们观察到父系种系也有很强的贡献趋势 (p = .052)。我们还发现，与在男性中广泛观察到的情况相反，女性显示出完整的识别记忆 (p = . 001）经过 3 个月的 CCH，揭示了疾病进展期间认知影响方面迄今未确认的性别二态性。总的来说，我们的研究结果强烈暗示母体生殖细胞的表观遗传变化，由我们重复的全身低氧刺激诱导，有助于改进分化程序，能够在成年男性第一代后代中建立痴呆症恢复表型。（PsycInfo 数据库记录 (c) 2023 APA，保留所有权利）。有助于改进分化程序，能够在成年男性第一代后代中建立抗痴呆表型。（PsycInfo 数据库记录 (c) 2023 APA，保留所有权利）。有助于改进分化程序，能够在成年男性第一代后代中建立抗痴呆表型。（PsycInfo 数据库记录 (c) 2023 APA，保留所有权利）。