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
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..View full abstract
The authors wish to thank Professors Niels C. Danbolt (University of Oslo, Norway) and David V. Pow (The University of Newcastle, Australia) for their generous gifts of EAAT antibodies, as well as Monash Micro Imaging (Monash University, Australia). CJZ was in receipt of an Australian Postgraduate Award, and PMB is a NH&MRC Senior Principal Research Fellow.