scholarly journals Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marco Benevento ◽  
Charlotte A. Oomen ◽  
Alexa E. Horner ◽  
Houshang Amiri ◽  
Tessa Jacobs ◽  
...  
Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Aleah Holmes ◽  
Yan Xu ◽  
Juneyoung Lee ◽  
Liang Zhu ◽  
Venugopal Reddy Venna ◽  
...  

Background: Social isolation (SI) and loneliness are risk factors for stroke. Epidemiological studies have shown that women tend to have a higher risk of stroke at later age and elderly women are more likely to be isolated. The mechanisms underlying the detrimental effects of SI have not been well studied in older females. We hypothesized that SI in aged female mice would lead to impaired post-stroke recovery and could lead to differential regulation of microRNAs (miRNAs). Methods: In this study, aged C57BL/6N female mice were subjected to a 60-minute middle cerebral artery occlusion (MCAO) and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. Infarct size, mortality and recovery was assessed using open field, the adhesive-tape removal task and the Y-maze test. MiRNAs were comprehensively analyzed by miRNAome analysis on stroke brain, and changes in hippocampal cell proliferation was assessed from perfused brain sections. Results: Importantly, SI immediately after stroke led to significantly larger tissue loss and higher mortality in aged females, it also significantly delayed motor/sensory recovery in the adhesive removal test and impaired overall locomotor activity. In addition, these mice also demonstrated worse post-stroke cognitive function. In parallel, brains of these mice showed reduced miR-297a-3p expression and increased miR-18a-3p and miR-200c-3p expression with SI compared to PH cohort and reduced hippocampal cell proliferation. Conclusion: The results from this study suggest that SI after stroke can increase mortality and significantly impair post-stroke recovery in aged female mice. These worse outcomes are in parallel to the significant changes in several miRNAs and reduced hippocampal cell proliferation.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Courtney Stewart ◽  
Aditya Panta ◽  
Taylor Branyan ◽  
Farida Sohrabji

Background: Post-stroke depression (PSD) occurs in one-third of stroke survivors, is more prevalent in women, and negatively impacts quality of life and recovery. Our previous work showed that acyclic middle-aged female rats display depressive behaviors after stroke, and IV treatment with mir363-3p attenuates these behaviors. Serotonin has been implicated in affective behaviors, and loss of this neurotransmitter is also associated with decreased neurogenesis in the hippocampus. The present study determined (a) whether stroke affected tryptophan, a gut metabolite, and precursor for serotonin, and cell proliferation in the hippocampus and (b) whether serum tryptophan levels and hippocampal cell proliferation was restored by mir363-3p. Methods: Ischemic stroke was induced by stereotaxic delivery of endothelin-1 to the MCA of middle-aged female rats. Animals received a single injection of mir363-3p or scrambled oligos 4h after stroke. Depressive-like behaviors were assessed by the Effort-based sucrose consumption test, Social Interaction and Forced Swim Test 3 months after stroke. Blood was collected at termination. Serum tryptophan levels were quantified by ELISA. Bacterial composition was analyzed by 16S sequencing of fecal samples. Ki67 immunohistochemistry was performed on brain tissue collected at termination and quantified within the dentate gyrus by two blind observers. Results: Animals subjected to stroke exhibited depressive-like behaviors and had decreased tryptophan levels as compared to sham treated animals. This is also accompanied by microbiota dysbiosis as measured by an elevated ratio of Firmicutes to Bacteroidetes. Mir363-3p treatment increased tryptophan levels as compared to scrambled controls and were no different from sham (non-stroke) animals. Moreover, miR363-3p treated rats exhibit a significantly more dentate gyrus-specific Ki67 expression a proliferation marker. Conclusions: Together, these data indicate that miR363-3p attenuates post stroke depression via a mechanism that prevents microbiota dysbiosis and increases hippocampal cell proliferation.


2007 ◽  
Vol 23 (3) ◽  
pp. 131-135 ◽  
Author(s):  
Guang Qiu ◽  
Daiga M. Helmeste ◽  
Asanka N. Samaranayake ◽  
Wui-Man Lau ◽  
Tatia M. C. Lee ◽  
...  

Neuroscience ◽  
2013 ◽  
Vol 255 ◽  
pp. 76-85 ◽  
Author(s):  
Y. Pan ◽  
M. Li ◽  
X. Yi ◽  
Q. Zhao ◽  
C. Lieberwirth ◽  
...  

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