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Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790554/ https://www.ncbi.nlm.nih.gov/pubmed/35170835 http://dx.doi.org/10.1002/alz.12616 |
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author | Belmonte, Krystal Courtney D. Holmgren, Eleanor B. Wills, Tiffany A. Gidday, Jeff M. |
author_facet | Belmonte, Krystal Courtney D. Holmgren, Eleanor B. Wills, Tiffany A. Gidday, Jeff M. |
author_sort | Belmonte, Krystal Courtney D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9790554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97905542022-12-28 Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment Belmonte, Krystal Courtney D. Holmgren, Eleanor B. Wills, Tiffany A. Gidday, Jeff M. Alzheimers Dement Featured Articles 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. John Wiley and Sons Inc. 2022-02-16 2022-10 /pmc/articles/PMC9790554/ /pubmed/35170835 http://dx.doi.org/10.1002/alz.12616 Text en © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Featured Articles Belmonte, Krystal Courtney D. Holmgren, Eleanor B. Wills, Tiffany A. Gidday, Jeff M. Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title | Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title_full | Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title_fullStr | Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title_full_unstemmed | Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title_short | Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
title_sort | epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment |
topic | Featured Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790554/ https://www.ncbi.nlm.nih.gov/pubmed/35170835 http://dx.doi.org/10.1002/alz.12616 |
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