Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen–glucose deprivation in neurons

• We model oxygen and glucose deprivation (OGD) in cultured primary cerebral cortical neurons of fetal mice.
• CART55–102 provides neuroprotection on OGD-neurons by decreasing ROS.
• CART55–102 increases the activity of complex II in OGD-neurons.
• Our results indicate the neuroprotective mechanism of CART55–102 during OGD-induced oxidative damage.

The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55–102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen–glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55–102 were most significant at 0.4 nM. These results indicated that CART55–102 suppressed neurotoxicity and enhanced neuronal survival after oxygen–glucose deprivation. CART55–102 (0.4 nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen–glucose deprived neurons. In summary, CART55–102 suppressed oxidative stress in oxygen–glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55–102 as an antioxidant drug.