Gender difference in epileptic seizure and neuropsychiatric behavior abnormalities induced by kainic acid in rats
Objective To observe the neuropsychiatric behavioral performance of kainic acid(KA)-induced epilepsy rats;investigate gender differences in acute seizure and behavioral performance tasks relating to sense,motor,learning,and memory in the remission phase;and explore the potential neurobiological mechanisms of action.Methods Healthy SD rats aged 4 weeks were randomly divided into control and model groups,with 22 rats in each group(11 males and 11 females).An epileptic rat model was induced by intraperitoneal injection of KA.Seizure latency and frequency within 2 hours of KA injection were observed,seizure grade was assessed using the Racine grade standard,and a cortical electroencephalogram(EEG)was recorded.Behavioral performance was observed in a series of tasks including open field testing,balance beam walking,elevated plus maze,Y-maze,and novel object recognition.The level of GABA in the hippocampus was detected by ELISA,injury to hippocampal neurons was observed by Nissl staining,and the protein expression of synapsin-1 and synaptotagmin 1 in the hippocampus were detected by Western Blot.Results Both male and female rats presented typical epileptic behaviors after KA injection.However,compared with the effects in males,the latency of the first seizure(P=0.014)and Ⅳ～Ⅴ grading in female model rats were more pronounced(P＜0.01),and the frequency of epileptic seizures within 2 hours was significantly reduced(P=0.019).In the open field testing,KA-induced epileptic rats presented more motor but fewer hedonic behaviors,as indicated by the decrease in total movement distance in the central area,compared with the control group.Moreover,grooming frequency was significantly reduced in the female model rats compared with not only that in the control but also that in male model rats(P＜0.01).The model rats spent more time completing and had a higher score in the balance beam walking task,indicating their poorer stability and balance.In the elevated plus maze,the exploration times of male model rats in the closed arm was increased.The preference index of rats for the novel arm or object decreased in the Y-maze and novel object recognition,suggesting impairments to their learning and memory abilities.Moreover,neuronal injuries were found in the hippocampus of the model rats that were accompanied with a decline in GABA concentration and protein expression of synapsin-1 and synaptotagmin 1,with no gender differences.Conclusions Intraperitoneal injection of KA successfully induced an epilepsy rat model.However,there was a gender difference in the characters of acute seizures and performance of sensory,motor,and learning memory during epileptic remission.There was no gender differences in the hippocampal GABA concentration or expression of synaptic plasticity-related proteins,and thus no evidence was found for the mechanisms underlying the gender differences.
epilepsymale and femalelearning and memoryKAGABAEEGrats
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