Department of Ophthalmology, Louisiana State University School of Medicine, LSUHSC, New Orleans, Louisiana, USA.
Department of Physiology, Louisiana State University School of Medicine, LSUHSC, New Orleans, Louisiana, USA.
Alzheimers Dement. 2022 Oct;18(10):1711-1720. doi: 10.1002/alz.12616. Epub 2022 Feb 16.
Epigenetic stimuli induce beneficial or detrimental changes in gene expression, and consequently, phenotype. Some of these phenotypes can manifest across the lifespan-and even in subsequent generations. Here, we used a mouse model of vascular cognitive impairment and dementia (VCID) to determine whether epigenetically induced resilience to specific dementia-related phenotypes is heritable by first-generation progeny.
Our systemic epigenetic therapy consisted of 2 months of repetitive hypoxic "conditioning" (RHC) prior to chronic cerebral hypoperfusion in adult C57BL/6J mice. Resultant changes in object recognition memory and hippocampal long-term potentiation (LTP) were assessed 3 and 4 months later, respectively.
Hypoperfusion-induced memory/plasticity deficits were abrogated by RHC. Moreover, similarly robust dementia resilience was documented in untreated cerebral hypoperfused animals derived from RHC-treated parents.
Our results in experimental VCID underscore the efficacy of epigenetics-based treatments to prevent memory loss, and demonstrate for the first time the heritability of an induced resilience to dementia.
表观遗传刺激可导致基因表达和表型产生有益或有害的变化。其中一些表型可以跨越生命历程出现，甚至在后代中出现。在这里，我们使用血管性认知障碍和痴呆（VCID）的小鼠模型来确定通过第一代后代是否可以遗传到针对特定与痴呆相关的表型的具有弹性的表观遗传诱导。
我们的系统性表观遗传治疗包括在成年 C57BL/6J 小鼠慢性大脑低灌注前进行 2 个月的重复缺氧“适应”（RHC）。分别在 3 个月和 4 个月后评估物体识别记忆和海马长时程增强（LTP）的变化。
RHC 消除了低灌注引起的记忆/可塑性缺陷。此外，在未接受 RHC 治疗的来自 RHC 治疗父母的大脑低灌注动物中，也记录到了同样强大的痴呆症抗药性。
我们在实验性 VCID 中的结果强调了基于表观遗传的治疗预防记忆丧失的功效，并首次证明了对痴呆症的诱导抗性的遗传性。
