Oxygen Radicals Elicit Paralysis and Collapse of Spinal Cord Neuron Growth Cones upon Exposure to Proinflammatory CytokinesReportar como inadecuado

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BioMed Research InternationalVolume 2014 2014, Article ID 191767, 20 pages

Research ArticleDepartment of Chemistry and Biochemistry, University of Alaska Fairbanks, 900 Yukon Drive, Reichardt Building, Room 194, Fairbanks, AK 99775-6150, USA

Received 16 October 2013; Revised 25 February 2014; Accepted 11 March 2014; Published 23 June 2014

Academic Editor: Tullia Maraldi

Copyright © 2014 Thomas B. Kuhn. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


A persistent inflammatory and oxidative stress is a hallmark of most chronic CNS pathologies Alzheimer’s ALS as well as the aging CNS orchestrated by the proinflammatory cytokines tumor necrosis factor alpha TNFα and interleukin-1 beta IL-1β. Loss of the integrity and plasticity of neuronal morphology and connectivity comprises an early step in neuronal degeneration and ultimate decline of cognitive function. We examined in vitro whether TNFα or IL-1β impaired morphology and motility of growth cones in spinal cord neuron cultures. TNFα and IL-1β paralyzed growth cone motility and induced growth cone collapse in a dose-dependent manner reflected by complete attenuation of neurite outgrowth. Scavenging reactive oxygen species ROS or inhibiting NADPH oxidase activity rescued loss of neuronal motility and morphology. TNFα and IL-1β provoked rapid, NOX-mediated generation of ROS in advancing growth cones, which preceded paralysis of motility and collapse of morphology. Increases in ROS intermediates were accompanied by an aberrant, nonproductive reorganization of actin filaments. These findings suggest that NADPH oxidase serves as a pivotal source of oxidative stress in neurons and together with disruption of actin filament reorganization contributes to the progressive degeneration of neuronal morphology in the diseased or aging CNS.

Autor: Thomas B. Kuhn

Fuente: https://www.hindawi.com/


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