Dynamic Changes of Astrocytes in the Hippocampus of Krushinsky–Molodkina Rats during Audiogenic Kindling

The studies of epileptogenesis have revealed not only a dysregulationof excitatory and inhibitory neurotransmission, but also pronouncedalterations in the astrocyte functioning. Here we explored how theestablishment of temporal lobe epilepsy (TLE) affected the astrocytesin the hippocampus of Krushinsky–Molodkina (KM) rats geneticallyprone to audiogenic seizures (AGS). To reproduce the different stagesof epileptogenesis, we used audiogenic kindling (daily AGS stimulations)of three durations: (1) 7 days, the initial stage; (2) 14 days,when the neurochemical and behavioral signs of TLE are almost stabilized;(3) 23 days, after which TLE in KM rats is fully established. NaïveKM rats without any AGS experience were used as a control. The expressionof such astrocyte markers, as glial fibrillary acidic protein (GFAP),excitatory amino acid transporters EAAT1 and 2, aquaporin 4 (AQP4), andaldolase C (AldoC), was analyzed. Our data demonstrated that GFAPexpression was unchanged after 7 AGS, but significantly upregulatedafter both 14 and 23 AGS indicating the development of reactiveastrogliosis. Similar dynamics was observed for AldoC, one of themain metabolic astrocyte proteins. EAAT1 expression was not affectedby kindling, while EAAT2 was significantly downregulated after 23AGS. Analysis of AQP4 revealed a significant decrease of expressionalready after 7 AGS which persisted during further kindling progression.Thus, our data revealed that audiogenic kindling of KM rats inducedastroglia aberrations similar to those observed in human epileptichippocampus and animal models of TLE.