Spinal anterior horn has the capacity to self-regenerate in am...

The exact host environment necessary for neural regeneration in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. We first focused on the extracellular matrix proteins in ALS model mice during development of the disease and then attempted to examine whether regeneration occurs in the ALS spinal cord under regenerative conditions. A progressive increase in gamma1 laminin (a promoter of regeneration) and a progressive decrease in semaphorin3A (Sema3A; an inhibitor of regeneration) were observed, mainly in the neuropil of the spinal anterior horn from 15 to 18 weeks, when astrocytes began to express both gamma1 laminin and Sema3A. On the other hand, a progressive increase in growth-associated protein 43 (GAP43; synaptic regeneration site) and a progressive decrease in synaptotagmin1 (actual synaptic bouton) were observed in the same areas of the spinal anterior horn from 15 to 18 weeks. Thus, the present data suggest that, although the spinal anterior horn in ALS models loses motor neurons, it initially possesses the capacity to self-regenerate but displays a progressive loss of ability to regenerate new effective synapses. (c) 2009 Wiley-Liss, Inc.