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Published on: February 24, 2023
MicroRNA-8126-Mediated Antioxidant Stress Attenuates Isoflurane-Induced Hippocampal Neurotoxicity in Developing Rats
Wen Pan1, WenFeng Xiao2, LingShuai Xue3
1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610044, China.
Objective:
To investigate the effect of microRNA-8126 (miR-8126) on isoflurane-induced hippocampal neurotoxicity in rats.
Methods:
A rat isoflurane nerve injury model was constructed. The expression of miR-8126 in the hippocampal region of normal and injured rats was measured by qRT-PCR; synaptic density protein-95, PAK-3 (p21-activated kinase-3) and apoptosis-related proteins cytochrome C, cleaved caspase-3, and cleaved PARP were detected by Western blot. The Cytochrome C, cleaved-caspase-3, and cleaved PARP expression was detected by WB, as well as GSH-Px, CAT, SOD, and ROS.
Results:
miR-8126 was lowly expressed in the isoflurane-treated rat hippocampal region and in rat hippocampal neuronal cells, and the expression of apoptosis-related proteins and apoptosis levels were significantly increased, and neural activity, cell activity, and proliferation capacity were significantly decreased. Oxidative stress levels and ROS content were significantly increased; overexpression of miR-8126 in the rat hippocampal region significantly inhibited oxidative stress and apoptosis. Overexpression of miR-8126 in rat hippocampal neural progenitor cells significantly increased cell activity, proliferative capacity, and significantly smaller mitochondrial size and it decreased ROS content and oxidative stress levels and apoptosis-related protein expression compared to isoflurane-treated cells; while inhibition of miR-8126 expression in rat hippocampal neuronal cells significantly decreased cell activity, proliferative capacity, and mitochondrial size compared to the control group. In contrast, inhibition of miR-8126 expression in rat hippocampal neuronal cells resulted in a further decrease in cell activity, proliferation capacity, and significantly larger mitochondrial size and increased expression of apoptosis-related proteins compared with the control group. miR-8126 regulates the activity of rat hippocampal neuronal cells by targeting ATF4.
Conclusions:
miR-8126 attenuates isoflurane-induced hippocampal neurotoxicity in rats by mediating antioxidative stress.
Insights
MicroRNA-8126 (miR-8126) protects against isoflurane-induced neurotoxicity in rat hippocampus. Overexpression of miR-8126 reduces apoptosis and oxidative stress, preserving neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Isoflurane anesthesia can induce hippocampal neurotoxicity, impacting neuronal function and survival.
- MicroRNAs (miRNAs) play crucial roles in regulating cellular processes, including neuronal development and response to injury.
- Understanding the specific roles of miRNAs in anesthetic-induced neurotoxicity is essential for developing protective strategies.
Purpose of the Study:
- To investigate the protective effect of microRNA-8126 (miR-8126) against isoflurane-induced hippocampal neurotoxicity in a rat model.
- To elucidate the underlying mechanisms, including the regulation of apoptosis and oxidative stress.
Main Methods:
- A rat model of isoflurane-induced hippocampal injury was established.
- Quantitative real-time PCR (qRT-PCR) was used to measure miR-8126 expression.
- Western blotting was employed to assess the levels of synaptic proteins, apoptosis markers (cytochrome C, cleaved caspase-3, cleaved PARP), and oxidative stress indicators (GSH-Px, CAT, SOD, ROS).
- Experiments involved both overexpression and inhibition of miR-8126 in vivo and in vitro.
Main Results:
- miR-8126 expression was significantly downregulated in the hippocampus of rats exposed to isoflurane.
- Isoflurane exposure led to increased apoptosis, decreased neural and cell activity, reduced proliferation, and elevated oxidative stress (ROS).
- Overexpression of miR-8126 attenuated isoflurane-induced neurotoxicity by reducing oxidative stress and apoptosis, and improving cell viability and mitochondrial function.
- Inhibition of miR-8126 exacerbated these negative effects.
Conclusions:
- MicroRNA-8126 plays a significant protective role against isoflurane-induced hippocampal neurotoxicity in rats.
- miR-8126 exerts its neuroprotective effects by mediating antioxidative stress pathways.
- Targeting miR-8126 represents a potential therapeutic strategy for mitigating anesthetic-induced brain injury.
