Mitochondrial activity in different regions of the brain at the onset of streptozotocin-induced diabetes in rats
Diabetes affects a variety of tissues including the central nervous system; moreover, some evidence indicates that memory and learning processes are disrupted. Also, oxidative stress triggers alterations in different tissues including the brain. Recent studies indicate mitochondria dysfunction is a pivotal factor for neuron damage. Therefore, we studied mitochondrial activity in three brain regions at early type I—diabetes induction. Isolated mitochondria from normal hippocampus, cortex and cerebellum revealed different rates of oxygen consumption, but similar respiratory controls. Oxygen consumption in basal state 4 significantly increased in the mitochondria from all three brain regions from diabetic rats. No relevant differences were observed in the activity of respiratory complexes, but hippocampal mitochondrial membrane potential was reduced. However, ATP content, mitochondrial cytochrome c, and protein levels of β-tubulin III, synaptophysin, and glutamine synthase were similar in brain regions from normal and diabetic rats. In addition, no differences in total glutathione levels were observed between normal and diabetic rat brain regions. Our results indicated that different regions of the brain have specific metabolic responses. The changes in mitochondrial activity we observed at early diabetes induction did not appear to cause metabolic alterations, but they might appear at later stages. Longer-term streptozotocin treatment studies must be done to elucidate the impact of hyperglycemia in brain metabolism and the function of specific brain regions.
KeywordsMitochondria Hippocampus Brain cortex Cerebellum Diabetes Oxidative stress
The authors would like to thank Mr. G. Sánchez-Chávez for technical assistance, Mr. Diego Barjau for helping in some experiments. We also acknowledge to the Animal, Computational, and Supporting Facilities Units. This research was supported in part by a grant from Dirección General de Asuntos del Personal Académico/Programa de Apoyo de Investigación e Innovación Tecnológica/UNAM/DGAPA/PAPIIT-IG200216. Osorio-Paz received a doctoral scholarship from CONACyT México (263808/221053) enrolled in the Biochemistry PhD program at UNAM.
IO-P participated in the design of the experiments, writing the manuscript and carried out the experiments of mitochondrial activity. GP-R developed the western blot experiments, and participated in the discussion. JEH-R measured the GSH levels and ROS production. SUC help in the studies of mitochondrial activity, discussion and writing the manuscript. RS designed, coordinated the research and wrote the paper, funding acquisition.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving animal and human participants
All procedures were carried out in agreement with the Mexican Institute of Health Research (DOF. NOM-062-ZOO-1999) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH publication No. 80-23, revised 1996). The protocol was approved by the Institutional Committee for the Care and Use of Laboratory Animals of the Institute of Cellular Physiology of the Autonomous National University of Mexico (CICUAL Comité Institucional para el Cuidado y Uso de los Animales de Laboratorio del Instituto de Fisiología Celular de la Universidad Nacional Autónoma de México) under Protocol Number RSS18-14; this was done in accordance with the Office of Laboratory Animal Welfare (OLAW), Assurance Number A5281-01. All efforts were made to minimize animal suffering and to reduce the number of rats used.
- 11.Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M (2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75(13):1195–1202. https://doi.org/10.1212/WNL.0b013e3181f4d7f8 CrossRefPubMedGoogle Scholar
- 12.Wang WT, Lee P, Yeh HW, Smirnova IV, Choi IY (2012) Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo (1)H MR spectroscopy at 9.4 T. J Neurochem 121(3):407–417. https://doi.org/10.1111/j.1471-4159.2012.07698.x CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Trautschold IL, Schweitzer G (1988) Adenosine 5′triphosphate. UV-Method with hexokinase and glucose-6-phosphate dehydrogenase. In: Bergmeyer HU (ed) Bergmeyer enzymatic methods VII: 346–357, vol VII, 3rd edn. Verlag Chemie, WeinheimGoogle Scholar
- 33.Sasaki-Hamada S, Sacai H, Oka JI (2012) Diabetes onset influences hippocampal synaptic plasticity in streptozotocin-treated rats. Neuroscience 27:293–304. https://doi.org/10.1016/j.neuroscience.2012.09.081 CrossRefGoogle Scholar
- 42.Cardoso S, Santos RX, Correia SC, Carvalho C, Santos MS, Baldeiras I, Oliveira CR, Moreira P (2013) Insulin-induced recurrent hypoglycemia exacerbates diabetic brain mitochondrial dysfunction and oxidative imbalance. Neurobiol Dis 49:1–12. https://doi.org/10.1016/j.nbd.2012.08.008 CrossRefPubMedGoogle Scholar