Altering TGF-β signaling pathway: An approach to halt pentylenetetrazole-induced epileptogenesis in mice
Journal Title: The 2nd Annual Meeting of International Center for Neuroscience Research - Year 2021, Vol 2, Issue 1
Abstract
Epilepsy is illustrated by persistent predisposition of the brain to generate seizures and considered as one of the most common, chronic, neurological disorder affecting around 1% of the individuals worldwide. A growing body of advanced researches now points a link between inflammation and various epilepsy syndromes, reflecting both an inflammatory state inside the epileptic brain along with increased permeability of the blood–brain barrier, heading towards enhanced neuronal excitability. The probable contribution of TGF-β in epileptogenesis is reinforced by animal studies viewing TGF-β up-regulation as measure of inflammatory reaction in the brains of kindled animals that are exposed to status epilepticus. The main focus of this study was to investigate the potental relationship between the TGF-β associated genes and epilepsy which will aid in confirming that up regulation of TGF-β genes might be one of the underlying cause of epilepsy. A novel anticonvulsant [E/Z] isoxylitones was used to treat epileptic seizures along with standard antiepileptic drugs (AEDs) diazepam and valproic acid in pentylenetetrazoleinduced kindling model of mice. To confirm aforementioned evidences, expression levels of TGF-β, TRAF6 and JNK3 genes along with inflammatory cytokine interleukin-1β (IL-1 β) were analyzed. It was observed that as compared to the PTZ-control group, there was a significant decrease in the response of seizures observed in [E/Z] isoxylitones treated group. Furthermore, expressions of these genes were significantly reduced in [E/Z] isoxylitones and standard AEDs treated groups. It is concluded that, TGF-β signaling pathway can be a potential subcellular target for reducing seizure duration and associated neuronal death in epilepsy and [E/Z] isoxylitones is an effective way to achieve this therapeutic target.
Authors and Affiliations
Maha Shahid, Uzair Nisar, Farzana Shaheen, Atta ur Rahman, Muhammad Iqbal Choudhary, Maryam Askani, Shabana Usman Simjee
Keywords
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