Maternal repetitive hypoxia prior to mating confers epigenetic resilience to memory impairment in male progeny.
Maternal repetitive hypoxia prior to mating confers epigenetic resilience to memory impairment in male progeny.
复制标题
交配前母体反复缺氧赋予雄性后代记忆障碍的表观遗传恢复能力。
DOI：
10.1037/bne0000554
复制
发表时间：
2023
影响因子：
1.9
通讯作者：
Gidday,JeffreyM
中科院分区：
文献类型：
--
作者：
Broyles,EmreyE;Corell,DavidH;Gidday,JeffreyM
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发现，通过新的物体识别测试评估，父母双方的重复缺氧条件（RHC）导致成年后代对识别记忆丧失的恢复能力的表观遗传、代际传递。本研究在相同的模型中进行，以确定父母一方或双方的RHC治疗是否需要在代际间赋予痴呆恢复能力。我们发现遗传恢复力在雄性3个月的CCH是由母亲介导的(p=。006)。统计上，我们观察到父系生殖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，女性表现出完整的识别记忆(p=。001)在CCH 3个月后，揭示了在疾病进展期间认知影响方面迄今未被识别的性别二态性。总的来说，我们的研究结果强烈暗示了母体生殖细胞的表观遗传变化，由我们的重复系统性缺氧刺激诱导，有助于修改分化程序，能够在成年雄性第一代后代中建立抗痴呆表型。
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.