Energy management and mitochondrial dynamics in cerebral cortex during endotoxemia

Abstract

Mitochondria play an essential role in inflammatory processes such as sepsis or endotoxemia, contributing to organ-cellular redox metabolism, emerging as the energy hub of the cell, and as an important center of action of second messengers. In this work, we aimed to elucidate the energy state, redox balance, and mitochondrial remodeling status in cerebral cortex in an experimental model of endotoxemia. Female Sprague-Dawley rats were subjected to a single dose of LPS (ip 8 mg kg−1 body weight) for 6 h. State 3 O2 consumption was observed increased, ATP production and P/O ratio were observed decreased, probably indicating an inefficient oxidative phosphorylation process. O2− production and both systemic and tissue NO markers were observed increased in treated animals. The existence of nitrated proteins suggests an alteration in the local redox balance and possible harmful effects over energetic processes. Increases in PGC-1α and mtTFA expression, and in OPA-1 expression, suggest an increase in de novo formation of mitochondria and fusion of pre-existing mitochondria. The observed elongation of mitochondria correlates with the occurrence of mild mitochondrial dysfunction and increased levels of systemic NO. Our work presents novel results that contribute to unravel the mechanism by which the triad endotoxemia-redox homeostasis-energy management interact in the cerebral cortex, leading to propose a relevant mechanism for future developing therapeutics with the aim of preserving this organ from inflammatory and oxidative damage.