Epigenetic Conditioning Induces Intergenerational Resilience To Dementia In A Mouse Model Of Vascular Cognitive Impairment
Alzheimer's and Dementia
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
Belmonte, Krystal Courtney D.; Holmgren, Eleanor B.; Wills, Tiffany A.; and Gidday, Jeff M., "Epigenetic Conditioning Induces Intergenerational Resilience To Dementia In A Mouse Model Of Vascular Cognitive Impairment" (2022). School of Graduate Studies Faculty Publications. 52.