Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia

Abstract Evidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (...

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Autores principales:	Nicholas Don-Doncow, Lotte Vanherle, Frank Matthes, Sine Kragh Petersen, Hana Matuskova, Sara Rattik, Anetta Härtlova, Anja Meissner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/1745737e9e5c4f2da50b435a4a85b4c2
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spelling	oai:doaj.org-article:1745737e9e5c4f2da50b435a4a85b4c22021-12-02T16:34:04ZSimvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia10.1038/s41514-021-00071-w2056-3973https://doaj.org/article/1745737e9e5c4f2da50b435a4a85b4c22021-08-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00071-whttps://doaj.org/toc/2056-3973Abstract Evidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (BP)-lowering properties. How their ability to modify immune responses affects cognitive function is unknown. Here, we examined the effect of chronic hypercholesterolemia on inflammation and memory function in Apolipoprotein E (ApoE) knockout mice and normocholesterolemic wild-type mice. Chronic hypercholesterolemia that was accompanied by moderate blood pressure elevations associated with apparent immune system activation characterized by increases in circulating pro-inflammatory Ly6Chi monocytes in ApoE-/- mice. The persistent low-grade immune activation that is associated with chronic hypercholesterolemia facilitates the infiltration of pro-inflammatory Ly6Chi monocytes into the brain of aged ApoE-/- but not wild-type mice, and links to memory dysfunction. Therapeutic cholesterol-lowering through simvastatin reduced systemic and neuro-inflammation, and the occurrence of memory deficits in aged ApoE-/- mice with chronic hypercholesterolemia. BP-lowering therapy alone (i.e., hydralazine) attenuated some neuro-inflammatory signatures but not the occurrence of memory deficits. Our study suggests a link between chronic hypercholesterolemia, myeloid cell activation and neuro-inflammation with memory impairment and encourages cholesterol-lowering therapy as safe strategy to control hypercholesterolemia-associated memory decline during ageing.Nicholas Don-DoncowLotte VanherleFrank MatthesSine Kragh PetersenHana MatuskovaSara RattikAnetta HärtlovaAnja MeissnerNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Nicholas Don-Doncow Lotte Vanherle Frank Matthes Sine Kragh Petersen Hana Matuskova Sara Rattik Anetta Härtlova Anja Meissner Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
description	Abstract Evidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (BP)-lowering properties. How their ability to modify immune responses affects cognitive function is unknown. Here, we examined the effect of chronic hypercholesterolemia on inflammation and memory function in Apolipoprotein E (ApoE) knockout mice and normocholesterolemic wild-type mice. Chronic hypercholesterolemia that was accompanied by moderate blood pressure elevations associated with apparent immune system activation characterized by increases in circulating pro-inflammatory Ly6Chi monocytes in ApoE-/- mice. The persistent low-grade immune activation that is associated with chronic hypercholesterolemia facilitates the infiltration of pro-inflammatory Ly6Chi monocytes into the brain of aged ApoE-/- but not wild-type mice, and links to memory dysfunction. Therapeutic cholesterol-lowering through simvastatin reduced systemic and neuro-inflammation, and the occurrence of memory deficits in aged ApoE-/- mice with chronic hypercholesterolemia. BP-lowering therapy alone (i.e., hydralazine) attenuated some neuro-inflammatory signatures but not the occurrence of memory deficits. Our study suggests a link between chronic hypercholesterolemia, myeloid cell activation and neuro-inflammation with memory impairment and encourages cholesterol-lowering therapy as safe strategy to control hypercholesterolemia-associated memory decline during ageing.
format	article
author	Nicholas Don-Doncow Lotte Vanherle Frank Matthes Sine Kragh Petersen Hana Matuskova Sara Rattik Anetta Härtlova Anja Meissner
author_facet	Nicholas Don-Doncow Lotte Vanherle Frank Matthes Sine Kragh Petersen Hana Matuskova Sara Rattik Anetta Härtlova Anja Meissner
author_sort	Nicholas Don-Doncow
title	Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
title_short	Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
title_full	Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
title_fullStr	Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
title_full_unstemmed	Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
title_sort	simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1745737e9e5c4f2da50b435a4a85b4c2
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Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia

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