Combined excitotoxic-oxidative stress and the concept of non-cell autonomous pathology of ALS: Insights into motoneuron axonopathy and astrogliosis
Nicole Wallis, Chrissandra J Zagami, Philip M Beart, Ross D O'Shea
NEUROCHEMISTRY INTERNATIONAL | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2012
Non-cell autonomous pathology is widely accepted to determine the demise of motoneurons (MNs) in amyotrophic lateral sclerosis (ALS) with astrocytes, GFAP and glutamate transport suggested to play roles in reactive astrogliosis. Previously we described actions of excitotoxicity and oxidative stress to produce differential injury of motoneurons and astrocytes, respectively, and our goal here was to define patterns of MN injury and astrogliosis during a combined excitotoxic-oxidative injury since such a paradigm more closely models disease pathology. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that glutamate transport activity was maintained or incre..View full abstract
Awarded by NH & MRC (Australia)
Supported by NH & MRC (Australia) Project Grant (#509319) and Fellowship (PMB). NW acknowledges receipt of Postgraduate Scholarship from the Bethlehem Griffiths Research Foundation. Gift of EAAT2 antibody from David Pow (University of Queensland, Brisbane, Australia) is greatly appreciated.