Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Brain, behavior, and immunity - 117(2024) vom: 05. März, Seite 36-50 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Harrison, Mark A A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 07.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2023.12.033 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aging | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a Blood brain barrier | |
| 650 | 4 | |a Brain microvascular endothelial cells | |
| 650 | 4 | |a Cognitive decline | |
| 650 | 4 | |a Cytomegalovirus | |
| 650 | 4 | |a Dementia | |
| 650 | 4 | |a Metabolism | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Pathogen | |
| 700 | 1 | |a Morris, Sara L |e verfasserin |4 aut | |
| 700 | 1 | |a Rudman, Grace A |e verfasserin |4 aut | |
| 700 | 1 | |a Rittenhouse, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Monk, Chandler H |e verfasserin |4 aut | |
| 700 | 1 | |a Sakamuri, Siva S V P |e verfasserin |4 aut | |
| 700 | 1 | |a Mehedi Hasan, Md |e verfasserin |4 aut | |
| 700 | 1 | |a Shamima Khatun, Mst |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hanyun |e verfasserin |4 aut | |
| 700 | 1 | |a Garfinkel, Lucas P |e verfasserin |4 aut | |
| 700 | 1 | |a Norton, Elizabeth B |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sangku |e verfasserin |4 aut | |
| 700 | 1 | |a Kolls, Jay K |e verfasserin |4 aut | |
| 700 | 1 | |a Michal Jazwinski, S |e verfasserin |4 aut | |
| 700 | 1 | |a Mostany, Ricardo |e verfasserin |4 aut | |
| 700 | 1 | |a Katakam, Prasad V G |e verfasserin |4 aut | |
| 700 | 1 | |a Engler-Chiurazzi, Elizabeth B |e verfasserin |4 aut | |
| 700 | 1 | |a Zwezdaryk, Kevin J |e verfasserin |4 aut | |
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