Dual effects of carnosine on energy metabolism of cultured cortical astrocytes under normal and ischemic conditions

• Carnosine reduces OXPHOS of astrocytes under the normal growth condition.
• Astrocytes depend on glycolysis for ATP production in the recovery processafter OGD.
• Carnosine upregulates OXPHOS of astrocytes in the recovery process after OGD.
• Pyruvate may not be involved in the carnosine action on astrocyte energy metabolism.

ObjectiveThe aim of this study was to investigate the effects of carnosine on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions.MethodsThe Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions.ResultsUnder the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72 ± 1.59 pmol/min/μg protein and 3.95 ± 0.28 mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~ 80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~ 42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8 h of oxygen–glucose deprivation (OGD) followed by 24 h of recovery under the normal growth condition.ConclusionsCarnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury.