This abstract has been invited to present during the Investigators Workshop Platform poster session
Rationale: Epilepsy, the fourth most common neurological disorder, is characterized by spontaneous recurrent seizures. In Alzheimer's disease (AD), seizures also occur, where the incidence has been linked to disease progression in Alzheimer's disease (AD). Histology of surgically resected brain samples from patients with epilepsy have been reported to share some common pathologies with AD brains, such as hyperphosphorylated tau and the expression of amyloid precursor protein. These pathologies could directly contribute to the development of seizures in both diseases. Evidently, Fyn, a Src family kinase, interacts with tau leading to NMDAR-mediated neurodegeneration in animal models of AD. To date, it is not known if Fyn-tau interactions also play a role in seizure generation or seizure-associated pathologies in animal models of epilepsy or human epileptic patients. Mainly, it is not well understood if seizures could affect the formation of Fyn-tau interactions as the disease progresses. In this study, we evaluate the pattern of Fyn-tau pathology and their interaction in multiple experimental models of epilepsy as well as the human epileptic brain. Methods: We examined two mouse models; a single high dose of pentylenetetrazole (PTZ) (40mg/kg) as a seizure model and a repeated low dose of KA (5 mg/kg, i.p., at 30 min intervals) as an epilepsy model. Brains collected at 6h and 24h post-SE. We also used surgically resected temporal lobe from patients with epilepsy. Proximity ligation assay (PLA) for Fyn-tau interaction and immunohistochemistry (IHC) for gliosis, neurodegeneration, and Fyn-tau cellular localization were conducted. Results: We found that fyn-tau interaction, as detected by PLA, increased in mouse models compared to controls. Neurodegeneration and gliosis were also significantly elevated post-SE. Likewise, Fyn-tau interaction was significantly upregulated in human epileptic brains compared to age-matched control brains. Moreover, in the human epileptic brain, we observed higher expression of tau pathology and Fyn in neurons, and increased microgliosis, relative to controls. Conclusions: Our study demonstrates the upregulation of Fyn and tau interaction in both animal models of epilepsy and the human epileptic brain suggesting a role for Fyn-tau interaction in seizure-induced neurodegeneration and neuroinflammation. Thus, strategies disengaging the Fyn-tau interaction can promote the prevention and/or modification of epilepsy. Funding: Please list any funding that was received in support of this abstract.: This project was supported by Iowa State University-University of Iowa seed grant, Iowa, USA.