Combined excitotoxic-oxidative stress and the concept of non-cell autonomous pathology of ALS: Insights into motoneuron axonopathy and astrogliosis

Abstract

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..