Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [KA and APOE]

Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype Overall design: 3 KA-induced TLE model; 6 KA-induced TLE model and treated with KA; 6 KA-induced TLE model and treated with KA and APOE