Preferential pruning of inhibitory synapses by microglia contributes to alteration of the balance between excitatory and inhibitory synapses in the hippocampus in temporal lobe epilepsy

• DOI: 10.1111/cns.14224
• Publication Date: 2023-04-19T05:01:09Z
• Authors: Jianchen Fan; Xinyan Dong; Yejiao Tang; Xuehui Wang; Donghui Lin; Lifen Gong; Chen Chen; Jie Jiang; Weida Shen; Anyu Xu; Xiangnan Zhang; Yicheng Xie; Xin Huang; Linghui Zeng
• Keywords: Interneuron

Abstract Background A consensus has formed that neural circuits in the brain underlie pathogenesis of temporal lobe epilepsy (TLE). In particular, synaptic excitation/inhibition balance (E/I balance) been implicated shifting towards elevated excitation during development TLE. Methods Sprague Dawley (SD) rats were intraperitoneally subjected to kainic acid (KA) generate a model Next, electroencephalography (EEG) recording was applied verify stability and detectability spontaneous recurrent seizures (SRS) rats. Moreover, hippocampal slices from patients with mesial (mTLE) assessed using immunofluorescence determine alterations excitatory inhibitory synapses microglial phagocytosis. Results We found KA induced stable SRSs 14 days after status epilepticus (SE) onset. Furthermore, we discovered continuous increase epileptogenesis, where total area vesicular glutamate transporter 1 (vGluT1) rose considerably stratum radiatum (SR) cornu ammonis (CA1), lucidum (SL) CA3, polymorphic layer (PML) dentate gyrus (DG). contrast, decreased significantly, decarboxylase 65 (GAD65) SL PML diminishing enormously. microglia conducted active phagocytosis formation SRSs, especially PML. Finally, preferentially pruned both rat human slices, which contributed alteration subregions. Conclusions Our findings elaborately characterize demonstrate selectivity mediated by TLE, could strengthen comprehension TLE inspire potential therapeutic targets for treatment.