Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic

• OXPHOS ATP-producing capacity was compromised 7 days after diabetes onset.
• SOD mimic restored ATP generating capacity by increasing the OXPHOS proteins content.
• Observed upregulation of the glycolytic enzyme by diabetes was not affected by mimic.
• Mimic may achieve this beneficial effects by reducing O2− and/or increasing NO level.

Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity.To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level ≥12 mM.Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1α – the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1α to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated.To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder.