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Alteration of astrocyte markers and phosphorylation of tau protein in kainic acid-treated animal model of Temporal Lobe Epilepsy

  • Author / Creator
    Dahal, Abhishek
  • Kainic acid, 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 ~50million 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 kainic acid-treated animal model of mTLE. Our results reveal that levels/expression of various astrocytes markers such as GFAP, vimentin, S100β, Aldh1l1, but not GS, are differentially altered in the hippocampus of kainic acid-treated rats. The levels/expression of both A1(C3+) and A2(S100A10+)-like astrocytes are variably increased in kainic acid-treated rats. The hippocampal levels of total (Tau1 and Tau5) and phospho-tau (AT270 and PHF1) proteins are also transiently enhanced following kainic acid administration. Furthermore, the steady-state level and expression of cleaved-tau, which is evident in a subset of GFAP-positive astrocytes, are found to be increased in kainic acid-treated rats. These results, taken together, suggest a differential role for various astrocytic subpopulations and tau protein in kainic acid model of TLE and possibly in human mTLE pathogenesis.

  • Subjects / Keywords
  • Graduation date
    Fall 2022
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-040c-z538
  • License
    This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.