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| Effects of miR-146a on Brain Development and Cognitive Function in Offspring of Pregnant Rats with Electrical Ignition Seizures |
| MIERGULI Aimaite, et al |
| The People's Hospital of Xinjiang Uygur Autonomous Region / Xinjiang Clinical Medical Research Center for Stroke and Nervous System Rare Diseases, Xinjiang Urumqi 830001, China |
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Abstract Objective: To investigate the effect of miR-146a on the growth and cognitive function of offspring of pregnant rats with complete ignition of epilepsy. Methods: Female rats were divided into control, model, and miR-146a inhibitor groups, with 6 rats in each group. Rats in the control group were implanted with electrodes only, and rats in the model group were implanted with electrodes. Epilepsy was ignited by the constant current with a frequency of 60Hz, wave width of 1.0ms, and string length of 10s. And the rats in the miR-146a inhibitor group were implanted with electrodes, then, epilepsy was ignited, followed by miR-146a inhibitor administration (dose: 2 mg/kg), twice a week until delivery. The female rats were caged together with the male rats after successful seizure ignition, and the female rats were observed to be pregnant. After the litter was born, the timing of the roll-over reflex and grasp response was observed during the growth of the litter, and the miR-146a content in brain tissue was compared by RT-PCR. The litter was monitored for body weight and length, and after the litter was grown to 84 d, the Morris water maze test was performed to assess the cognitive function of the litter. Nissler staining was used to detect the neuronal status and Golgi staining to detect the dendritic spine density. Results: Compared with the control group, the content of miR-146a in the model group increased (P<0.01); compared with the model group, the content of miR-146a in the miR-146a inhibitor group decreased(P<0.01). Compared with the control group, the offspring rats in the model group of the righting reflex time increased(P<0.01), the grasping reaction time decreased (P<0.01), the body weight and body length reduced(P<0.001), the escape latency significantly increased (P<0.01), and the number of crossing the platform and swimming in the platform quadrant significantly decreased(P<0.01); the number of Nissl cells decreased, and the length and density of dendritic spines decreased (P<0.01). Compared with the model group, the offspring rats in the miR-146a inhibitor group increased, the righting reflex time decreased (P<0.001), and the grasping reaction time prolonged (P<0.01); the body weight and body length of the offspring increased (P<0.01), the escape latency reduced (P<0.01), the number of platform crossings and platform quadrant swimming increased (P<0.05); the number of Nissl cells increased, and the length and density of dendritic spines increased (P<0.05). Conclusion: The complete ignition of maternal epilepsy during pregnancy can increase the expression of miR-146a in the brain tissue of offspring rats. Reducing the expression of miR-146a can significantly promote the growth of offspring rats, promote the development of the central nervous system, increase the density and length of dendritic spines, and improve the long-term development of offspring rats’ cognitive function
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2023, Vol. 29 
