Proepileptic roles of astrocytes in mesial temporal lobe epilepsy with hippocampal sclerosis.

About 30% of patients with mesial temporal lobe epilepsy (mTLE), in which the hippocampus is the epileptic focus, is drug-resistant to existing antiepileptic drugs that target the modulation of neuronal activity. mTLE is commonly accompanied by the hippocampal sclerosis, which is primarily characterized by neuronal cell loss and chronic astrogliosis in hippocampal CA3 areas. It has been suggested that the changes in astrocytic function associated with hippocampal sclerosis contribute to epileptogenesis, but the underlying cellular and molecular mechanisms remain unclear. Here, we found that during the development of hippocampal sclerosis, some astrocytes migrate from CA3 to the dentate gyrus (DG) and upregulate the gene expression that could modulate neural activity related to the epileptic state. In intrahippocampal kainic acid (KA)-injected mTLE model mice, we found that some astrocytes migrate from CA3 to DG during the early-stage of hippocampal sclerosis after KA-injection. Then, we investigated the transcriptional profiles of the migrating astrocytes, finding an increased expression of genes that could result in hyperactivation of neurons. Thus, our findings reveal previously unknown changes in CA3 astrocytes during hippocampal sclerosis and propose astrocytes as a therapeutic target for mTLE.