Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
(2021) In npj Aging and Mechanisms of Disease 7.- 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... (More)
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.
(Less)
- author
- Don-Doncow, Nicholas LU ; Vanherle, Lotte LU ; Matthes, Frank LU ; Petersen, Sine Kragh ; Matuskova, Hana LU ; Rattik, Sara LU ; Härtlova, Anetta and Meissner, Anja LU
- organization
-
- Department of Experimental Medical Science
- Vascular Biology (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Cardiovascular Research - Translational Studies (research group)
- Cardiovascular Research - Cellular Metabolism and Inflammation (research group)
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- publishing date
- 2021-08-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- npj Aging and Mechanisms of Disease
- volume
- 7
- article number
- 19
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85111955341
- pmid:34349106
- ISSN
- 2056-3973
- DOI
- 10.1038/s41514-021-00071-w
- language
- English
- LU publication?
- yes
- id
- ea6582c5-0503-4bf2-8f5e-70f62c1f6861
- date added to LUP
- 2021-08-07 11:13:48
- date last changed
- 2024-06-16 16:35:41
@article{ea6582c5-0503-4bf2-8f5e-70f62c1f6861,
abstract = {{<p>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.</p>}},
author = {{Don-Doncow, Nicholas and Vanherle, Lotte and Matthes, Frank and Petersen, Sine Kragh and Matuskova, Hana and Rattik, Sara and Härtlova, Anetta and Meissner, Anja}},
issn = {{2056-3973}},
language = {{eng}},
month = {{08}},
publisher = {{Nature Publishing Group}},
series = {{npj Aging and Mechanisms of Disease}},
title = {{Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia}},
url = {{http://dx.doi.org/10.1038/s41514-021-00071-w}},
doi = {{10.1038/s41514-021-00071-w}},
volume = {{7}},
year = {{2021}},
}