Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: Dynamic responses to depolarization and sensitivity to pioglitazone

Tristano Pancani, Katie L. Anderson, Nada M. Porter, Olivier Thibault

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Neuronal Ca2+ dyshomeostasis associated with cognitive impairment and mediated by changes in several Ca2+ sources has been seen in animal models of both aging and diabetes. In the periphery, dysregulation of intracellular Ca2+ signals may contribute to the development of insulin resistance. In the brain, while it is well-established that type 2 diabetes mellitus is a risk factor for the development of dementia in the elderly, it is not clear whether Ca2+ dysregulation might also affect insulin sensitivity and glucose utilization. Here we present a combination of imaging techniques testing the disappearance of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as an indication of glycolytic activity in neurons and astrocytes. Our work shows that glucose utilization at rest is greater in neurons compared to astrocytes, and ceases upon activation in neurons with little change in astrocytes. Pretreatment of hippocampal cultures with pioglitazone, a drug used in the treatment of type 2 diabetes, significantly reduced glycolytic activity in neurons and enhanced it in astrocytes. This series of experiments, including Fura-2 and NADH imaging, provides results that are consistent with the idea that Ca2+ levels may rapidly alter glycolytic activity, and that downstream events beyond Ca2+ dysregulation with aging, may alter cellular metabolism in the brain.

Original languageEnglish
Pages (from-to)548-558
Number of pages11
JournalCell Calcium
Volume50
Issue number6
DOIs
StatePublished - Dec 2011

Bibliographical note

Funding Information:
We wish to thank Ms. Jelena Popović and Mr. Michael Bridges for their technical expertise and assistance with the culture preparations. We thank Dr. Patrick Sullivan (University of Kentucky, Spinal Cord and Brain Injury Research and Department of Anatomy and Neurobiology) for his gift of rotenone. We also would like to thank Drs. Piascik and Hadley (University of Kentucky, Department of Molecular and Biomedical Pharmacology) for their critical reading of the manuscript and helpful discussions. These studies were supported by grants AG029268 , AG033649 , NCRR-P20-RR15592 , and a gift from the Neurosciences Education and Research Foundation .

Keywords

  • Brain aging
  • Calcium signaling
  • Glycolysis imaging
  • Metabolic dysregulation
  • Thiazolidinedione

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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