Degree Type

Thesis

Date of Award

2017

Degree Name

Master of Science

Department

Theses & dissertations (Interdisciplinary)

Major

Neuroscience

First Advisor

Thimmasettappa Thippeswamy

Abstract

Epilepsy is one of the four most common neurological disorders, which is characterized by unprovoked recurrent seizures. Fyn-tau interaction has been associated with neurodegenerative changes in Alzheimer's disease (AD). While the genetically ablated Tau appears to be protective against seizures in AD models, the roles of Fyn and tau in the early phase of epileptogenesis in seizure models are not clear. Particularly, it is still unknown whether a combination of Fyn and tau reduction can exert a more profound neuroprotective effect. Here, we demonstrate the effects of genetic deletion of Fyn and/or tau in the early phase of epileptogenesis using pentylenetetrazole (PTZ)-induced epilepsy mouse model. We examined three genetically engineered genotypes; Fyn-/-, Tau-/-, double mutant Fyn-/-+Tau-/- within the first 24h after seizure induction. All knockout mice reduced the severity of seizures and prolonged the latency to the onset convulsive seizures (CS), stage 3 and above with the most prominent effects observed in Tau-/- mice and double mutant Fyn-/-+ Tau-/- mice in contrast the wildtype (WT) control mice. The Fyn-/- mice, however, showed higher mortality, in < 20 min of seizure induction, in contrast to the other knockouts (KO) and the WT. Despite this unexpected finding, all KO groups immunohistochemically exhibited a reduction in hippocampal neurodegeneration and reactive gliosis. Also, in all KO mice, the parvalbumin-GABAergic interneurons in the hippocampus and entorhinal cortex were resistant to PTZ injection, while their numbers significantly reduced in the WT. In the hippocampus, the level of inwardly rectifying potassium (Kir 4.1) channels was significantly downregulated in the astrocytes in the WT mice treated with PTZ, while its level was unaffected in all KO groups. Overall, our results indicate that disabling the Fyn and/or tau displays neuroprotective effects against pathological changes in the hippocampus at the early phase of epileptogenesis.

Copyright Owner

Marson Rubianto Eka Putra

Language

en

File Format

application/pdf

File Size

82 pages

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