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Updated: Oct 3, 2025
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive
Krystal Courtney D Belmonte1,2, Eleanor B Holmgren3, Tiffany A Wills3,4
1Department of Ophthalmology, Louisiana State University School of Medicine, LSUHSC, New Orleans, Louisiana, USA.
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.
