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Carnosine ameliorates postoperative cognitive dysfunction of aged rats by limiting astrocytes pyroptosis.
- Source :
-
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [Neurotherapeutics] 2024 Jul; Vol. 21 (4), pp. e00359. Date of Electronic Publication: 2024 Apr 25. - Publication Year :
- 2024
-
Abstract
- Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, and neuroinflammation is a key hallmark. Recent studies suggest that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated astrocytes pyroptosis is involved in the regulation of neuroinflammation in many neurocognitive diseases, while its role in POCD remains obscure. Carnosine is a natural endogenous dipeptide with anti-inflammatory and neuroprotective effects. To explore the effect of carnosine on POCD and its mechanism, we established a POCD model by exploratory laparotomy in 24-month-old male Sprague-Dawley rats. We found that the administrated of carnosine notably attenuated surgery-induced NLRP3 inflammasome activation and pyroptosis in astrocytes, central inflammation, and neuronal damage in the hippocampus of aged rats. In addition, carnosine dramatically ameliorated the learning and memory deficits of surgery-induced aged rats. Then in the in vitro experiments, we stimulated primary astrocytes with lipopolysaccharide (LPS) after carnosine pretreatment. The results also showed that the application of carnosine alleviated the activation of the NLRP3 inflammasome, pyroptosis, and inflammatory response in astrocytes stimulated by LPS. Taken together, these findings suggest that carnosine improves POCD in aged rats via inhibiting NLRP3-mediated astrocytes pyroptosis and neuroinflammation.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Male
Rats
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Aging drug effects
Aging metabolism
Hippocampus drug effects
Hippocampus metabolism
Inflammasomes metabolism
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Neuroinflammatory Diseases metabolism
Neuroinflammatory Diseases drug therapy
Cells, Cultured
Carnosine pharmacology
Astrocytes drug effects
Astrocytes metabolism
Pyroptosis drug effects
Pyroptosis physiology
Rats, Sprague-Dawley
Postoperative Cognitive Complications metabolism
Postoperative Cognitive Complications prevention & control
Postoperative Cognitive Complications drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1878-7479
- Volume :
- 21
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 38664193
- Full Text :
- https://doi.org/10.1016/j.neurot.2024.e00359