Protective Role of UCP2 in Oxidative Stress and Apoptosis during the Silent Phase of an Experimental Model of Epilepsy Induced by Pilocarpine.

Abstract

Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure-induced excitotoxicity cell death and mitochondria impairment. The present study is aimed at investigating the role of UCP2, a ROS negative regulator, in the neuroprotection after cholinergic insult. Our data demonstrated that UCP2 expression was augmented in the rat hippocampus 3 days after status epilepticus (SE), reaching a peak on the fifth day, then returning to basal levels. Concomitantly, phospho-AKT expression levels were higher in the hippocampus during the early silent phase (5 days after SE). Additionally, it was demonstrated that the blockade of UCP2 by antisense oligonucleotides (ASO) in SE rats successfully diminished both UCP2 mRNA and protein contents. SE ASO rats presented increased mitochondrial proapoptotic factor expression, caspase-3 activity, inflammatory cytokine expression, and ROS formation. Moreover, ASO treatment diminished p-AKT expression and antioxidant enzyme activities after pilocarpine insult. In conclusion, the present results highlight the neuroprotective actions of UCP2, acting in the inhibition of apoptotic factors and oxidative stress, to increase neuron survival after SE onset.

• Authors: Marina Rascio Henriques Dutra, Regiane Dos Santos Feliciano, Kalil Ribeiro Jacinto, Telma Luciana Furtado Gouveia, Eduardo Brigidio, Andrey Jorge Serra, Mariana Morris, Maria da Graça Naffah-Mazzacoratti, José Antônio Silva Jr
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2018 Pg. 6736721 ( 2018) ISSN: 1942-0994 [Electronic] United States
• PMID: 30159115 (Publication Type: Journal Article)

Chemical References

• Ucp2 protein, rat
• Uncoupling Protein 2
• Pilocarpine

Topics

• Animals
• Apoptosis (physiology)
• Disease Models, Animal
• Male
• Oxidative Stress (drug effects, physiology)
• Pilocarpine
• Rats
• Rats, Wistar
• Status Epilepticus (chemically induced, metabolism, pathology)
• Uncoupling Protein 2 (metabolism)