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Differential production of reactive oxygen species in distinct brain regions of hypoglycemic mice

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Abstract

Hypoglycemia is a serious complication of insulin therapy in patients suffering from type 1 Diabetes Mellitus. Severe hypoglycemia leading to coma (isoelectricity) induces massive neuronal death in vulnerable brain regions such as the hippocampus, the striatum and the cerebral cortex. It has been suggested that the production of reactive oxygen species (ROS) and oxidative stress is involved in hypoglycemic brain damage, and that ROS generation is stimulated by glucose reintroduction (GR) after the hypoglycemic coma. However, the distribution of ROS in discrete brain regions has not been studied in detail. Using the oxidation sensitive marker dihydroethidium (DHE) we have investigated the distribution of ROS in different regions of the mouse brain during prolonged severe hypoglycemia without isoelectricity, as well as the effect of GR on ROS levels. Results show that ROS generation increases in the hippocampus, the cerebral cortex and the striatum after prolonged severe hypoglycemia before the coma. The hippocampus showed the largest increases in ROS levels. GR further stimulated ROS production in the hippocampus and the striatum while in the cerebral cortex, only the somatosensory and parietal areas were significantly affected by GR. Results suggest that ROS are differentially produced during the hypoglycemic insult and that a different response to GR is present among distinct brain regions.

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Acknowledgments

The present study was supported by CONACYT grant S-112179 to LM. The authors thank Gabriel Orozco for his help with confocal images and Francisco Pérez Eugenio for his computer technical support.

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Authors and Affiliations

  1. División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F, 04510, México

    Leticia Amador-Alvarado, Teresa Montiel & Lourdes Massieu

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  1. Leticia Amador-Alvarado
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  2. Teresa Montiel
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  3. Lourdes Massieu
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Correspondence to Lourdes Massieu.

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Amador-Alvarado, L., Montiel, T. & Massieu, L. Differential production of reactive oxygen species in distinct brain regions of hypoglycemic mice. Metab Brain Dis 29, 711–719 (2014). https://doi.org/10.1007/s11011-014-9508-5

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