miR‐365a‐3p Alleviates Isoflurane‐Induced Neuroinflammation and Cognitive Impairment by Targeting MyD88 to Inhibit NF‐κB Signaling
Abstract
Isoflurane (ISO) exposure is associated with neuroinflammation and postoperative cognitive dysfunction (POCD) in aged populations, although the underlying mechanisms remain unclear. This study aimed to determine whether ISO‐induced cognitive decline involves miR‐365a‐3p and its downstream signaling targets. Aged rats were exposed to ISO to establish a POCD model. Cognitive and motor functions were evaluated using Morris water maze tests and neurological scoring. The expression of miR‐365a‐3p, inflammatory factors, synaptic proteins, and apoptotic markers in the hippocampus was measured by qRT‐PCR, ELISA, and Western blotting. In vitro, LPS‐treated BV‐2 microglia were co‐cultured with differentiated SH‐SY5Y neurons to assess neuronal apoptosis rate (by flow cytometry) and synaptic integrity. Dual‐luciferase reporter assays verified the direct interaction between miR‐365a‐3p and MyD88. ISO exposure reduced hippocampal miR‐365a‐3p, resulting in memory/motor deficits, increased pro‐inflammatory factors, microglial activation, synaptic protein loss, and neuronal apoptosis. Adding extra miR‐365a‐3p reversed these problems. LPS treatment reduced miR‐365a‐3p expression and enhanced pro‐inflammatory cytokine production in BV‐2 cells, which subsequently induced apoptosis in co‐cultured neurons and impaired synaptic integrity. These conditions were reversed by miR‐365a‐3p overexpression. Mechanistically, miR‐365a‐3p directly targeted MyD88, inhibiting its expression and downstream NF‐κB activation. MyD88 overexpression reversed protective effects of miR‐365a‐3p on inflammation and synaptic function. ISO causes POCD by reducing miR‐365a‐3p, which protects the brain by blocking MyD88/NF‐κB. Boosting miR‐365a‐3p may represent a potential strategy to help prevent ISO‐related brain harm in elderly patients, warranting further translational investigation.
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MajorThe cited work was retracted on 2023-03-01 (notice 10.1016/j.heliyon.2023.e14265), before this paper was published (2025-08-07). Its authors could have known.
Cited work 10.1016/j.heliyon.2023.e14265 · retracted 2023-03-01 · notice 10.1016/j.heliyon.2023.e14265 · this paper published 2025-08-07
“10.1016/j.heliyon.2023.e14265”
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InfoThe cited work was retracted on 2026-09-16 (notice 10.1080/15376516.2026.2732286), not before this paper was published (2025-08-07).
Cited work 10.1080/15376516.2022.2042881 · retracted 2026-09-16 · notice 10.1080/15376516.2026.2732286 · this paper published 2025-08-07
“10.1080/15376516.2022.2042881”
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- Authors
- Bai, S., & Shi, P.
- Affiliations
- Yan'an University (CN)
- Corresponding author
- Shi, Peng
- ORCID
- Shi, Peng
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2025-08-07
- Volume
- 79
- Issue
- 5
- Pages
- e70025-e70025
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W4413048812
- Cited by
- 6
- References
- 31
- Citations by year
- 2026: 6
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-365a-3p, isoflurane, postoperative cognitive dysfunction, neuroinflammation, MyD88, NF-κB signaling, hippocampus, microglial activation, neuronal apoptosis, synaptic integrity, LPS, microRNA, cognitive impairment
- MeSH terms
- Postoperative Cognitive Complications, Neuroinflammatory Diseases, Animals, Hippocampus, Humans, Isoflurane, Male, Neurons, Signal Transduction, NF-kappa B, Rats, Sprague-Dawley, Apoptosis, Microglia, Anesthetics, Inhalation, Coculture Techniques, MicroRNAs, Mice, Rats, Myeloid Differentiation Factor 88, Cognitive Dysfunction
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