Hyperglycemia Induces Oxidative Stress and Impairs Axonal Transport Rates in Mice
Open Access
- 18 October 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (10), e13463
- https://doi.org/10.1371/journal.pone.0013463
Abstract
While hyperglycemia-induced oxidative stress damages peripheral neurons, technical limitations have, in part, prevented in vivo studies to determine the effect of hyperglycemia on the neurons in the central nervous system (CNS). While olfactory dysfunction is indicated in diabetes, the effect of hyperglycemia on olfactory receptor neurons (ORNs) remains unknown. In this study, we utilized manganese enhanced MRI (MEMRI) to assess the impact of hyperglycemia on axonal transport rates in ORNs. We hypothesize that (i) hyperglycemia induces oxidative stress and is associated with reduced axonal transport rates in the ORNs and (ii) hyperglycemia-induced oxidative stress activates the p38 MAPK pathway in association with phosphorylation of tau protein leading to the axonal transport deficits. T1-weighted MEMRI imaging was used to determine axonal transport rates post-streptozotocin injection in wildtype (WT) and superoxide dismutase 2 (SOD2) overexpressing C57Bl/6 mice. SOD2 overexpression reduces mitochondrial superoxide load. Dihydroethidium staining was used to quantify the reactive oxygen species (ROS), specifically, superoxide (SO). Protein and gene expression levels were determined using western blotting and Q-PCR analysis, respectively. STZ-treated WT mice exhibited significantly reduced axonal transport rates and significantly higher levels of ROS, phosphorylated p38 MAPK and tau protein as compared to the WT vehicle treated controls and STZ-treated SOD2 mice. The gene expression levels of p38 MAPK and tau remained unchanged. Increased oxidative stress in STZ-treated WT hyperglycemic mice activates the p38 MAPK pathway in association with phosphorylation of tau and attenuates axonal transport rates in the olfactory system. In STZ-treated SOD-overexpressing hyperglycemic mice in which superoxide levels are reduced, these deficits are reversed.This publication has 35 references indexed in Scilit:
- Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's DiseasePLOS ONE, 2010
- Mitochondrial superoxide plays a crucial role in the development of mitochondrial dysfunction during high glucose exposure in rat renal proximal tubular cellsFree Radical Biology & Medicine, 2009
- Sensory Neurons and Schwann Cells Respond to Oxidative Stress by Increasing Antioxidant Defense MechanismsAntioxidants and Redox Signaling, 2009
- Diabetic neuropathies: components of etiologyJournal of the Peripheral Nervous System, 2008
- Age-related decrease in axonal transport measured by MR imaging in vivoNeuroImage, 2008
- SOD2 protects neurons from injury in cell culture and animal models of diabetic neuropathyExperimental Neurology, 2007
- In vivo axonal transport rates decrease in a mouse model of Alzheimer's diseaseNeuroImage, 2007
- A role for mitogen‐activated protein kinases in the etiology of diabetic neuropathyThe FASEB Journal, 2001
- Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cellsFree Radical Biology & Medicine, 2001
- Methamphetamine toxicity is attenuated in mice that overexpress human manganese superoxide dismutaseBrain Research, 2000