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

Aleah Holmes,Juneyoung Lee,Yan Xu,Liang Zhu,Michael E Maniskas,Louise D Mccullough,Venugopal Reddy Venna

doi:10.3390/ijms22010099

Abstract

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.

Highlights

Stroke is the fifth leading cause of death and the primary cause of adult disability in the United States [1]
In order to investigate whether post-stroke Social isolation (SI) could influence ischemic injury size; mice were subjected to a 60 min MCAO and reperfusion
At 15 days post-stroke, animals were euthanized, and brain tissue loss was evaluated with cresyl violet (CV) staining (Figure 1B)

Summary

Introduction

Stroke is the fifth leading cause of death and the primary cause of adult disability in the United States [1]. The incidence of stroke will continue to rise [2]. Data from the United States (US) Census shows an increase in the number of people living alone from 17% of households in 1970 to 27% in 2012, and this trend is likely to increase, especially in elderly women [8,9]. Widowed or single older men and women are a demographic group susceptible to neurological disorders [10]. They represent more than 30% of men and 56% of women aged 65 years or older living in the US [9]. The mechanisms mediating the detrimental effects of SI remain largely unknown

Methods

Results

Conclusion