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

The studies of epileptogenesis have revealed not only a dysregulation of excitatory and inhibitory neurotransmission, but also pronounced alterations in the astrocyte functioning. Here we explored how the establishment of temporal lobe epilepsy (TLE) affected the astrocytes in the hippocampus of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). To reproduce the different stages of 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. Naïve KM rats without any AGS experience were used as a control. The expression of such astrocyte markers, as glial fibrillary acidic protein (GFAP), excitatory amino acid transporters EAAT1 and 2, aquaporin 4 (AQP4), and aldolase C (AldoC), was analyzed. Our data demonstrated that GFAP expression was unchanged after 7 AGS, but significantly upregulated after both 14 and 23 AGS indicating the development of reactive astrogliosis. Similar dynamics was observed for AldoC, one of the main metabolic astrocyte proteins. EAAT1 expression was not affected by kindling, while EAAT2 was significantly downregulated after 23 AGS. Analysis of AQP4 revealed a significant decrease of expression already after 7 AGS which persisted during further kindling progression. Thus, our data revealed that audiogenic kindling of KM rats induced astroglia aberrations similar to those observed in human epileptic hippocampus and animal models of TLE.