Dataset Information

(R,S)-Ketamine Promotes Striatal Neurogenesis and Sensorimotor Recovery Through Improving Poststroke Depression-Mediated Decrease in Atrial Natriuretic Peptide.

ABSTRACT:

Background

Poststroke social isolation could worsen poststroke depression and dampen neurogenesis. (R,S)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation-mediated depressive-like behaviors and sensorimotor recovery remain unclear.

Methods

Mice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days postischemia. ISO mice received 2 weeks of (R,S)-ketamine treatment starting at 14 days postischemia. Primary ependymal epithelial cells and choroid plexus epithelial cells were cultured and treated with recombinant human atrial natriuretic peptide (ANP) protein.

Results

The poststroke social isolation model was successfully established using middle cerebral artery occlusion combined with poststroke isolation, as demonstrated by a more prominent depression-like phenotype in ISO mice compared with pair-housed mice. (R,S)-ketamine reversed ISO-mediated depressive-like behaviors and increased ANP levels in the atrium. The depression-like phenotype was negatively correlated with ANP levels in both the atrium and plasma. Atrial GLP-1 and GLP-1 receptor signaling was essential to the promoting effects of (R,S)-ketamine on the synthesis and secretion of ANP from the atrium in ISO mice. (R,S)-ketamine also increased ANP and TGF-β1 levels in the choroid plexus of ISO mice. Recombinant human ANP increased TGF-β1 levels in both the primarily cultured ependymal epithelial cells and choroid plexus epithelial cells. Furthermore, (R,S)-ketamine increased TGF-β1 levels in the ischemic hemisphere and promoted striatal neurogenesis and sensorimotor recovery via ANP in ISO mice.

Conclusions

(R,S)-ketamine alleviated poststroke ISO-mediated depressive-like behaviors and thus promoted striatal neurogenesis and sensorimotor recovery via ANP.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9616367 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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(<i>R,S</i>)-Ketamine Promotes Striatal Neurogenesis and Sensorimotor Recovery Through Improving Poststroke Depression-Mediated Decrease in Atrial Natriuretic Peptide.

Zhang Yujing Y Xie Bing B Yuan Yin Y Zhou Ting T Xiao Ping P Wu Yuming Y Shang You Y Yuan Shiying S Zhang Jiancheng J

Biological psychiatry global open science 20210422 2

<h4>Background</h4>Poststroke social isolation could worsen poststroke depression and dampen neurogenesis. (<i>R,S</i>)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation-mediated depressive-like behaviors and sensorimotor recovery remain unclear.<h4>Methods</h4>Mice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days pos ...[more]

PMID: 36324997

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Project description:Background Several studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta-analysis to investigate the efficacy and safety of SSRIs in poststroke recovery. Methods and Results In this meta-analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo-controlled trials in design and reported SSRIs' effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], -7.05 [95% CI, -11.78 to -2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, -1.45 [95% CI, -2.77 to -0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09-0.61]), dependence (WMD, 8.86 [95% CI, 1.23-16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, -0.79 [95% CI, -1.42 to -0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12-1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13-1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo. Conclusions Our study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well-conducted placebo-controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021285766.