Pre-symptomatic alterations in subcellular βCGRP distribution in motor neurons precede astrogliosis in ALS mice

In our study we investigated the pathology-related expression patterns of the two calcitonin gene-related peptide (CGRP) isoforms in spinal cord motor neurons of SOD1(G93A) mice, an animal model of the human motor neuron disease, amyotrophic lateral sclerosis (ALS). We found that alpha CGRP and beta CGRP gene expression and alpha CGRP immunoreactivity remained unaltered throughout disease, and alpha CGRP gene deficiency had no effect on disease progression. In contrast, beta CGRP immunoreactivity appeared at atypical sites in degenerating motor neuron cell bodies, axons, and dendrites already in the early pre-symptomatic disease phase around postnatal day 40. A close association of beta CGRP-containing dysmorphic dendritic structures with processes of activated astrocytes, in combination with a selective expression of the CGRP receptor by astrocytes, suggests that beta CGRP may function as a motor neuron-derived signaling molecule for astrocyte activation in ALS. (C) 2009 Elsevier Inc. All rights reserved.