Administration of Kainic Acid Differentially Alters Astrocyte Markers and Transiently Enhanced Phospho-tau Level in Adult Rat Hippocampus.

Kainic acid (KA), an analogue of the excitatory neurotransmitter glutamate, when administered systemically can trigger seizures and neuronal loss in a manner that mirrors the neuropathology of human mesial temporal lobe epilepsy (mTLE), which affects ∼50 million people globally. Evidence suggests that changes in astrocytes which precede neuronal damage play an important role in the degeneration of neurons and/or development of seizures in TLE pathogenesis. Additionally, a role for microtubule associated tau protein, involved in various neurodegenerative diseases including Alzheimer's disease, has also been suggested in the development of seizure and/or neurodegeneration in TLE pathogenesis. At present, possible alterations of different subtypes of astrocytes and their association, if any, with tau protein in TLE remain unclear. In this study, we evaluated alterations of different subtypes of astrocytes and phospho-/cleaved-tau levels in KA-treated rat model of TLE. Our results reveal that levels/expression of various astrocyte markers such as GFAP, vimentin, S100B, Aldh1L1, but not GS, are increased in the hippocampus of KA-treated rats. The levels/expression of both A1(C3+) and A2(S100A10+)-like astrocytes are also increased in KA-treated rats. Concurrently, the total (Tau1 and Tau5) and phospho-tau (AT270 and PHF1) levels are transiently enhanced following KA administration. Furthermore, the level/expression of cleaved-tau, which is apparent in a subset of GFAP-, S100B- and A2-positive astrocytes, are increased in KA-treated rats. These results, taken together, suggest a differential role for various astrocytic subpopulations and tau protein in the development of seizure and/or loss of neurons in KA model of TLE and possibly in human mTLE pathogenesis.