Journal article

Oxidative and Excitotoxic Insults Exert Differential Effects on Spinal Motoneurons and Astrocytic Glutamate Transporters: Implications for the Role of Astrogliosis in Amyotrophic Lateral Sclerosis

Chrissandra J Zagami, Philip M Beart, Nicole Wallis, Phillip Nagley, Ross D O'Shea

GLIA | WILEY | Published : 2009

Abstract

In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L-glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that EAAT activity was maintained initially, despite a loss of cellular viabili..

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