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Related Experiment Video

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(R,S)-Ketamine Promotes Striatal Neurogenesis and Sensorimotor Recovery Through Improving Poststroke

Yujing Zhang1, Bing Xie1, Yin Yuan1

  • 1Department of Critical Care Medicine and the Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Biological Psychiatry Global Open Science
|November 3, 2022
PubMed
Summary

(R,S)-ketamine treatment effectively reduced depression-like behaviors in mice after stroke and social isolation. This intervention promoted brain repair and improved motor function by increasing atrial natriuretic peptide (ANP) levels.

Keywords:
(R,S)-ketamineAtrial natriuretic peptideNeurogenesisPoststroke depressionSocial isolationTransforming growth factor-β

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Stroke Research

Background:

  • Poststroke social isolation can exacerbate depression and impair neurogenesis.
  • The antidepressant and neuroprotective effects of (R,S)-ketamine are known, but its role in social isolation-induced depression and sensorimotor recovery post-stroke is unclear.

Purpose of the Study:

  • To investigate the mechanisms by which (R,S)-ketamine alleviates depressive-like behaviors and improves sensorimotor function in a mouse model of poststroke social isolation.
  • To explore the role of atrial natriuretic peptide (ANP) in mediating these effects.

Main Methods:

  • A mouse model of transient middle cerebral artery occlusion was established, followed by social isolation (ISO) or pair-housing.
  • (R,S)-ketamine was administered to ISO mice. Atrial natriuretic peptide (ANP) and TGF-β1 levels were measured.
  • Primary ependymal and choroid plexus epithelial cells were treated with ANP.

Main Results:

  • Social isolation exacerbated depressive-like behaviors post-stroke.
  • (R,S)-ketamine treatment reversed these behaviors and increased ANP levels, which correlated negatively with depressive phenotype.
  • (R,S)-ketamine promoted neurogenesis and sensorimotor recovery via ANP, involving GLP-1 receptor signaling and increased TGF-β1.

Conclusions:

  • (R,S)-ketamine alleviates depressive-like behaviors associated with poststroke social isolation.
  • The therapeutic effects are mediated through the ANP pathway, promoting neurogenesis and sensorimotor recovery.