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Activating ryanodine receptor improves isoflurane-induced cognitive dysfunction.
Binwen Liu1, Xurui Zhu2, Qingyun Zhou1
1Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing 210008, China; Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
Brain Research Bulletin
|October 18, 2023
Summary
Caffeine, a ryanodine receptor agonist, may improve postoperative cognitive dysfunction (POCD) in mice. This study investigated caffeine
Area of Science:
- Neuroscience
- Anesthesiology
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) involves impaired memory and learning.
- Prolonged isoflurane anesthesia is a risk factor for POCD.
- Hippocampal ryanodine receptor (RyR) dysfunction may contribute to POCD.
Purpose of the Study:
- Investigate RyR3 expression in the hippocampus after isoflurane anesthesia.
- Evaluate caffeine's potential to improve POCD in mice.
- Identify molecular mechanisms underlying isoflurane-induced cognitive dysfunction.
Main Methods:
- Constructed a POCD mouse model using 6-hour isoflurane exposure.
- Administered caffeine (RyR agonist) to mice and Neuro-2a cells.
- Assessed cognitive function via fear conditioning and location memory tests.
- Utilized RT-PCR, Western blot, and bioinformatics analysis.
Main Results:
- Isoflurane anesthesia induced cognitive deficits and increased hippocampal RyR3 mRNA.
- Caffeine administration improved cognitive function in POCD mice.
- Caffeine corrected altered expression of cognitive-related proteins in N2a cells.
- Bioinformatics analysis implicated CaMKⅣ in the molecular mechanism.
Conclusions:
- Ryanodine receptor agonist caffeine shows potential for mitigating isoflurane-induced cognitive dysfunction.
- Caffeine may offer a therapeutic strategy for POCD.
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