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

Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain.
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DOI:
10.3390/ijms22010099
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发表时间:
2020-12-24
影响因子:
5.6
通讯作者:
Venna VR
Venna VR
中科院分区:
生物学2区
文献类型:
--
作者:
Holmes A;Xu Y;Lee J;Maniskas ME;Zhu L;McCullough LD;Venna VR

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社交孤立和孤独是中风的危险因素。老年妇女更容易被孤立。人口普查数据显示,在65岁以上的房主中,女性独居的可能性要大得多。然而,隔离的有害影响的潜在机制尚未在老年女性中得到很好的研究。在这项研究中,我们假设隔离会损害老年雌性小鼠中风后的恢复,导致大脑中的微RNA(miRNAs)失调,包括那些先前被证明参与社交隔离(SI)的微RNA。将老年C57 BL/6雌性小鼠进行60分钟的大脑中动脉闭塞,并在中风后立即随机分配至单次圈养(SI)或连续成对圈养(PH)15天。卒中后立即SI导致卒中后脑组织丢失明显更多,死亡率更高。此外,SI显着延迟运动和感觉的恢复和恶化的认知功能,相比PH。细胞增殖的减少被认为是在SI小鼠的齿状回溴脱氧尿苷(BrdU)标记评估。miRNAome数据分析揭示了大脑中几种miRNAs的变化,如miR-297 a-3 p和miR-200 c-3 p,它们已知调节参与细胞增殖的途径。总之,我们的数据表明,SI可导致老年女性中风后恢复不良,miRNA失调和海马细胞增殖减少。
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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