昆明医科大学学报2025,Vol.46Issue(12):40-48,9.DOI:10.12259/j.issn.2095-610X.S20251205
Glu/GABA调节神经递质平衡改善抽动秽语综合征大鼠模型行为异常的机制
Mechanism on Glu/GABA Regulating Neurotransmitter Balance to Improve Behavioral Abnormalities in Rat Models of Tourette Syndrome
摘要
Abstract
Objective To investigate the mechanism by which Glu/GABA regulation of neurotransmitter balance improves behavioral abnormalities in a rat model of Tourette syndrome(TS).Methods Forty-eight SPF-grade SD rats were randomly divided into four groups:normal control group,model group,Glu/GABA 1 group(10 mg/kg)and Glu/GABA 2 group(20 mg/kg),with 12 rats in each group.Except for the normal control group,the remaining rats received intraperitoneal injections of 250 mg/(kg·d)IDPN for 7 consecutive days to establish TS m odel.After successful model establishment,each group received gavage intervention for 6 weeks.Stereotyped behavior scores were assessed using blinded methods before intervention,at week 3,and week 6.Total spontaneous activity distance was detected using a video activity monitoring system.After intervention,brain tissue was harvested for HE staining to count neurons in the cortex,striatum,and thalamus,and transmission electron microscopy was used to observe myelin morphology.HPLC was used to detect Glu and GABA levels in brain tissues;immuno-fluorescence was used to determine their fluorescence intensity,so as to explore the effect of Glu/GABA on TS model rats.Results Stereotyped behavior scores and total spontaneous activity distance in the model group and Glu/GABA intervention groups were significantly higher than in the normal control group(P<0.05).After 6 weeks of intervention,stereotyped behavior scores and total spontaneous activity distance in Glu/GABA groups 1 and 2 were significantly reduced compared to the model group(P<0.001),with no statistical difference between the two intervention groups(P>0.05).Neuron counts in the cortex,striatum,and thalamus of the model group decreased,with myelin lamellae loosening and axonal damage.After Glu/GABA intervention,neuron counts recovered(P<0.01)and myelin structure improved.Compared with normal group,the model group showed significantly elevated brain Glu levels and fluorescence intensity,and significantly decreased GABA(P<0.01).Glu/GABA intervention reversed these changes(P<0.01).Conclusion Glu/GABA effectively reduces stereotyped behavior scores and spontaneous activity distance in TS model rats,repairs neuronal damage and myelin abnormalities in the cortex,striatum,and thalamus,and regulates brain Glu and GABA levels to normal balanced states,thereby exerting thera-peutic effects on TS.关键词
Glu/GABA/神经递质/抽动秽语综合征大鼠模型Key words
Glu/GABA/Neurotransmitter/Rat model of Tourette syndrome分类
医药卫生引用本文复制引用
DUAN Jingjing,DU Ningyu,XIAO Yan,LIU Xiang,CUI Junxia..Glu/GABA调节神经递质平衡改善抽动秽语综合征大鼠模型行为异常的机制[J].昆明医科大学学报,2025,46(12):40-48,9.基金项目
河北省中医药管理局中医药类科学研究基金(2024384) (2024384)