Epigenetic Conditioning Induces Intergenerational Resilience To Dementia In A Mouse Model Of Vascular Cognitive Impairment

Document Type

Article

Publication Date

2-16-2022

Publication Title

Alzheimer's and Dementia

Abstract

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.

First Page

1711

Last Page

1720

PubMed ID

35170835

Volume

18

Issue

10

Link to Full Text

Share

COinS