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

A. Stančić, V. Otašević, A. Janković, M. Vučetić, I. Ivanović-Burmazović, M. Filipović, A. Korać, M. Markelić, K. Veličković, I. Golić, B. Buzadžić and B. Korać
Brain Research Bulletin, 99 (2013), 27-33.

Abstract. 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.

Keywords: diabetes, hippocampus, SOD mimic, oxidative phosphorylation, glycolysis

IF: 2.974
IF5: 2.829
MNTR classification: M22


  title = {Molecular basis of hippocampal energy metabolism in diabetic rats: the effects of SOD mimic},
  author = {Stancic, Ana and Otasevic, Vesna and Jankovic, Aleksandra and Vucetic, Milica and Ivanovic-Burmazovic, Ivana and Filipovic, Milos R and Korac, Aleksandra and Markelic, Milica and Velickovic, Ksenija and Golic, Igor and Buzadzic, Biljana and Korac, Bato},
  journal = {Brain research bulletin},
  volume = {99},
  pages = {27--33},
  year = {2013}