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Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment
Author(s) -
Belmonte Krystal Courtney D.,
Holmgren Eleanor B.,
Wills Tiffany A.,
Gidday Jeff M.
Publication year - 2022
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12616
Subject(s) - epigenetics , dementia , hippocampal formation , phenotype , neuroscience , vascular dementia , long term potentiation , memory impairment , psychology , medicine , cognition , biology , genetics , gene , receptor , disease
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.