Related Experiment Video
Updated: Apr 16, 2026
Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
MiR-372-3p alleviates isoflurane-induced cognitive dysfunction by targeting STAT3 to mitigate neuroinflammation and
Mingpei Zhao1, Taifeng Li1, Qingni Zhang1
1Department of Anesthesiology, Naval Hospital No. 971 of the Chinese People's Liberation Army, Qingdao 266001, China.
Objective:
Isoflurane (ISO), a common anesthetic, can impair learning and memory, especially in the elderly. This study aims to determine whether miR-372-3p modulates neurocognitive dysfunction resulting from isoflurane anesthesia in experimental rats.
Methods:
SD rats were employed to construct the ISO treatment rat model. Spatial learning and memory were evaluated in rats using the Morris water maze (MWM). Hippocampal and microglial expression of miR-372-3p and STAT3 mRNA were quantified via qRT-PCR. ELISA assays detected pro-inflammatory cytokines, oxidative stress indicators, and Iba-1 levels in these tissues. The miR-372-3p/STAT3 regulatory axis was functionally validated through dual-luciferase reporter systems, RIP, and phenotypic rescue studies.
Results:
ISO treatment induced significant cognitive impairment in rats, concomitant with a marked downregulation of miR-372-3p expression in the hippocampal tissue. These deficits, evidenced by impaired spatial memory in the Morris water maze test, were effectively alleviated by the administration of a miR-372-3p agomir. Mechanistically, ISO triggered neuroinflammation, oxidative stress, and microglial activation (elevated Iba1) both in vivo and in BV-2 microglial cells. These detrimental effects were significantly mitigated by miR-372-3p overexpression. MiR-372-3p bound to the 3'UTR of STAT3 and suppressed its expression. Crucially, the protective effects of miR-372-3p against ISO-induced were effectively reversed by STAT3 overexpression.
Conclusion:
miR-372-3p downregulation acts as a critical contributor to ISO-induced cognitive dysfunction. Mechanistically, miR-372-3p's protective effects relate to the regulation of STAT3 signaling, with in vitro data confirming direct targeting and functional interplay. These results highlight the potential therapeutic value of the miR-372-3p/STAT3 axis in mitigating anesthesia-related neurotoxicity.
Insights
Isoflurane anesthesia impairs cognition by downregulating miR-372-3p, which normally protects against neuroinflammation and oxidative stress via the STAT3 pathway. Restoring miR-372-3p may combat anesthesia-induced cognitive deficits.
Area of Science:
- Neuroscience
- Molecular Biology
- Anesthesiology
Background:
- Isoflurane (ISO) anesthesia can negatively impact cognitive functions, particularly learning and memory.
- The elderly are especially vulnerable to these neurocognitive deficits induced by anesthesia.
Purpose of the Study:
- To investigate the role of miR-372-3p in isoflurane-induced neurocognitive dysfunction in rats.
- To elucidate the underlying molecular mechanisms involving the miR-372-3p/STAT3 axis.
Main Methods:
- Established an isoflurane-treated rat model and assessed cognitive function using the Morris water maze.
- Quantified miR-372-3p and STAT3 mRNA expression via qRT-PCR and measured inflammatory/oxidative markers using ELISA.
- Validated the miR-372-3p/STAT3 interaction using dual-luciferase reporter assays, RIP, and phenotypic rescue studies.
Main Results:
- Isoflurane exposure led to cognitive impairment and reduced hippocampal miR-372-3p levels.
- Overexpression of miR-372-3p ameliorated isoflurane-induced neuroinflammation, oxidative stress, and cognitive deficits.
- MiR-372-3p directly targets STAT3, suppressing its expression, and this interaction is crucial for the protective effects.
Conclusions:
- Downregulation of miR-372-3p is a key factor in isoflurane-induced cognitive impairment.
- The miR-372-3p/STAT3 signaling pathway plays a critical role in mediating anesthesia-related neurotoxicity.
- Targeting the miR-372-3p/STAT3 axis offers a potential therapeutic strategy against anesthesia-induced cognitive dysfunction.
