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Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress.
- Source :
-
Journal of Psychiatric Research . Feb2023, Vol. 158, p1-14. 14p. - Publication Year :
- 2023
-
Abstract
- Post-stroke chronic stress (PSCS) is generally associated with the poorer recovery and more pronounced cognitive dysfunction. Recent evidence has implied that S-ketamine can reduce suicidal ideation in treatment-resistant depression. In this current study, we aimed to investigate whether the administration of S-ketamine ameliorated cognitive deficits under PSCS conditions, which was established by a model combining middle cerebral artery occlusion (MCAO) and chronic restraint stress. Our data suggested that mice exposed to PSCS exhibited depression-like behavior and cognitive impairment, which coincided with astrocytosis as indicated by increased GFAP-positive cells and impairment of long-time potentiation (LTP) in the hippocampal CA1. Subanesthetic doses (10 mg/kg) of S-ketamine have significantly mitigated depression-like behaviors, cognitive deficits and LTP impairment, reduced astrocytosis, excessive GABA, and inflammatory factors, including NLRP3 and IL-18 in astrocytes in the CA1. Besides, neuroprotective effects induced by S-ketamine administration were found in vitro but could be partially reversed by an agonist of the NLRP3 nigericin. Our current data also suggests that the subanesthetic doses of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of PSCS. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223956
- Volume :
- 158
- Database :
- Academic Search Index
- Journal :
- Journal of Psychiatric Research
- Publication Type :
- Academic Journal
- Accession number :
- 161601583
- Full Text :
- https://doi.org/10.1016/j.jpsychires.2022.12.010