Lingling Xie1,2,3,4,5,6, Tianyi Li1,3,4,5,6, Xiaojie Song1,3,4,5,6, Hong Sun1,3,4,5,6, Jie Liu1,3,4,5,6, Jing Yang1,3,4,5,6, Wenjie Zhao1,3,4,5,6, Li Cheng2,3,4,5,6, Hengsheng Chen2,3,4,5,6, Benke Liu1,3,4,5,6, Wei Han1,3,4,5,6, Chen Yang1,3,4,5,6, Li Jiang1,2,3,4,5,6. 1. Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China. 2. Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China. 3. National Clinical Research Center for Child Health and Disorders, Chongqing, China. 4. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. 5. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. 6. Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Abstract
PURPOSE: To study the alteration of microglial subtypes, the representative markers of microglia, and the morphology of dendrites and dendritic spines after acute status epilepticus (SE) and during recurrent seizures. METHODS: A mouse kainate-induced SE model was used. Dendrites and dendritic spines of granule neurons in the dentate gyrus (DG) subregion and pyramidal neurons in the cornu ammonis (CA)1 and cornu ammonis (CA)3 subregions of the hippocampus were visualized by Golgi staining. Synaptic proteins were evaluated by Western blot analysis, and microglia and their markers were evaluated by flow cytometry. RESULTS: Extensive partial spine loss was observed in the dendrites of granule and pyramidal cells in the acute and early chronic stages of SE. In terms of spine loss, the thin and mushroom types predominated. Accompanying the spine loss in these two stages, the proportion of M1 microglia increased significantly with high CX3CR1 expression and low CD200R expression. However, at the transiting stage, the proportion of M2 microglia was increased dramatically, and high expression levels of CXCR3 on all microglia and CD68 on M1 microglia were observed. Morris water maze tests revealed significant learning and memory impairment in the chronic phase of epilepsy. CONCLUSION: Dendritic spines in the hippocampus and microglia in the central nevus system are dynamically altered in epilepsy during the establishment and maintenance of spontaneous seizures. Microglia may contribute to the spine loss and related learning and memory impairment.
PURPOSE: To study the alteration of microglial subtypes, the representative markers of microglia, and the morphology of dendrites and dendritic spines after acute status epilepticus (SE) and during recurrent seizures. METHODS: A mouse kainate-induced SE model was used. Dendrites and dendritic spines of granule neurons in the dentate gyrus (DG) subregion and pyramidal neurons in the cornu ammonis (CA)1 and cornu ammonis (CA)3 subregions of the hippocampus were visualized by Golgi staining. Synaptic proteins were evaluated by Western blot analysis, and microglia and their markers were evaluated by flow cytometry. RESULTS: Extensive partial spine loss was observed in the dendrites of granule and pyramidal cells in the acute and early chronic stages of SE. In terms of spine loss, the thin and mushroom types predominated. Accompanying the spine loss in these two stages, the proportion of M1 microglia increased significantly with high CX3CR1 expression and low CD200R expression. However, at the transiting stage, the proportion of M2 microglia was increased dramatically, and high expression levels of CXCR3 on all microglia and CD68 on M1 microglia were observed. Morris water maze tests revealed significant learning and memory impairment in the chronic phase of epilepsy. CONCLUSION: Dendritic spines in the hippocampus and microglia in the central nevus system are dynamically altered in epilepsy during the establishment and maintenance of spontaneous seizures. Microglia may contribute to the spine loss and related learning and memory impairment.
Entities:
Keywords:
Microglia; dendrite; kainate; mice; status epilepticus