Isoflurane Promotes Neuroinflammation and Induces Cognitive Impairment Through the miR-3099-5p/AQP4 Axis
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Xiangshuo Meng1, Pengzhou Tang2, Shengquan Cheng3
1Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu, China.
Background:
Isoflurane is an inhalational anesthetic widely used in clinical practice. However, its potential neurotoxic mechanisms have not been fully elucidated. Recent studies have found that miR-3099-5p is stably expressed in the brain and is closely associated with neural injury, neurodevelopment, and stem cell differentiation.
Method:
This study utilized an isoflurane-treated SD rat model to assess the effects of isoflurane on the spatial learning and memory capabilities of the rats through the Morris water maze experiment system. ELISA technology was employed to measure the levels of inflammatory factors, while the thiobarbituric acid reactive substance method and WST-1/NBT colorimetric method were used to determine oxidative stress indicators. Furthermore, qRT-PCR technology was applied to detect gene expression levels, and the regulatory relationships between target genes were further examined through dual-luciferase reporter gene assays.
Result:
Exposure to isoflurane can lead to cognitive dysfunction in rats, accompanied by an upregulation of miR-3099-5p expression. Additionally, inhibiting miR-3099-5p not only significantly improves these cognitive deficits but also attenuates the isoflurane-induced inflammatory response of microglia and oxidative stress, with the mechanism being through direct targeting and inhibition of AQP4 expression.
Conclusion:
miR-3099-5p mediates isoflurane-induced neurotoxicity via AQP4 regulation. Its inhibition alleviates cognitive impairment and neuroinflammation, providing a novel therapeutic target for anesthesia-related neural damage and potential neuroprotective drug development.
Insights
Isoflurane anesthesia can impair cognitive function by increasing miR-3099-5p, which targets AQP4. Inhibiting miR-3099-5p protects against isoflurane-induced neurotoxicity and cognitive deficits.
Area of Science:
- Neuroscience
- Anesthesiology
- Molecular Biology
Background:
- Isoflurane is a common inhalational anesthetic with incompletely understood neurotoxic effects.
- MicroRNA-3099-5p (miR-3099-5p) is implicated in neural injury, development, and differentiation.
Purpose of the Study:
- To investigate the role of miR-3099-5p in isoflurane-induced neurotoxicity.
- To elucidate the underlying molecular mechanisms, including AQP4 regulation.
Main Methods:
- Utilized an isoflurane-treated Sprague-Dawley rat model.
- Assessed cognitive function using the Morris water maze.
- Measured inflammatory factors (ELISA), oxidative stress (TBARS, WST-1/NBT), and gene expression (qRT-PCR).
- Investigated gene regulation via dual-luciferase reporter assays.
Main Results:
- Isoflurane exposure impaired spatial learning and memory in rats.
- miR-3099-5p expression was upregulated following isoflurane exposure.
- Inhibiting miR-3099-5p ameliorated cognitive deficits, neuroinflammation, and oxidative stress.
- This protective effect was mediated by direct targeting and inhibition of Aquaporin-4 (AQP4) expression.
Conclusions:
- miR-3099-5p plays a critical role in mediating isoflurane-induced neurotoxicity through AQP4 regulation.
- Inhibition of miR-3099-5p offers a potential therapeutic strategy for mitigating anesthesia-related neural damage.
- This finding opens avenues for developing neuroprotective drugs against anesthesia-induced cognitive impairment.
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