Protective Role of UCP2 against Oxidative Stress through Survival Signaling Pathway in Acute Epilepsy induced by Pilocarpine in Rats

Abstract

Neuroprotection is a desirable process in many human neurological disorders, yet complexes mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure‐induced excitotoxicity cell death, and mitochondria impairment is also observed in this model. The present study was designed to verify neuroprotection of UCP2 against hippocampal epilepsy, using Real‐time PCR, immunohistochemistry, Western blot and RNA silencing. Herein, we demonstrated that rats subjected to an animal model of epilepsy induced by pilocarpine had increased levels of UCP2 mRNA expression in the acute phase. Additionally, the brains of rats injected with pilocarpine showed increased pro‐inflammatory makers mRNA expression. Moreover, these rats presented augmented p‐AKT expression only in the acute phase of the protocol, concomitantly with UCP2 mRNA augmentation. Rats treated with pilocarpine also presented an increase in oxidative stress, marked by damage caused by lipid peroxidation, higher levels of protein carbonyl, and a decrease in the levels of antioxidant enzymes, SOD and catalase. On the other hand, when pilocarpine‐treated rats received ASO therapy for UCP2, the number of seizures observed in the acute phase was increased compared to pilocarpine only injected rats. UCP2 silencing were able to worsening the oxidative stress parameters and diminishing p‐AKT expression. In conclusion, our study demonstrated that UCP2 might have neuroprotection after pilocarpine insult in hippocampi of rats.Support or Funding InformationThe authors wish to thank the CNPQ (308067/2014‐2) and FAPESP, PRONEX, Instituto Nacional de Neurociência Translacional, (INNT‐MCT), and CAPES.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.