Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well...

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Main Authors: Aleah Holmes, Yan Xu, Juneyoung Lee, Michael E. Maniskas, Liang Zhu, Louise D. McCullough, Venugopal Reddy Venna
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/1/99
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author Aleah Holmes
Yan Xu
Juneyoung Lee
Michael E. Maniskas
Liang Zhu
Louise D. McCullough
Venugopal Reddy Venna
author_facet Aleah Holmes
Yan Xu
Juneyoung Lee
Michael E. Maniskas
Liang Zhu
Louise D. McCullough
Venugopal Reddy Venna
author_sort Aleah Holmes
collection DOAJ
description Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.
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spelling doaj.art-18571034787f4f77a8862876cc747d5d2023-11-21T02:21:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012219910.3390/ijms22010099Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice BrainAleah Holmes0Yan Xu1Juneyoung Lee2Michael E. Maniskas3Liang Zhu4Louise D. McCullough5Venugopal Reddy Venna6Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USABiostatistics and Epidemiology Research Design Core, Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USASocial isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.https://www.mdpi.com/1422-0067/22/1/99ischemic strokesocial isolationmiRNAneurogenesisaging
spellingShingle Aleah Holmes
Yan Xu
Juneyoung Lee
Michael E. Maniskas
Liang Zhu
Louise D. McCullough
Venugopal Reddy Venna
Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
International Journal of Molecular Sciences
ischemic stroke
social isolation
miRNA
neurogenesis
aging
title Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
title_full Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
title_fullStr Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
title_full_unstemmed Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
title_short Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain
title_sort post stroke social isolation reduces cell proliferation in the dentate gyrus and alters mirna profiles in the aged female mice brain
topic ischemic stroke
social isolation
miRNA
neurogenesis
aging
url https://www.mdpi.com/1422-0067/22/1/99
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