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 SOD1G93A mice, an animal model of the human motor neuron disease, amyotrophic lateral sclerosis (ALS). We found that αCGRP and βCGRP gene expression and αCGRP immunoreactivity remained unaltered throughout disease, and αCGRP gene deficiency had no effect on disease progression. In contrast, βCGRP 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 βCGRP-containing dysmorphic dendritic structures with processes of activated astrocytes, in combination with a selective expression of the CGRP receptor by astrocytes, suggests that βCGRP may function as a motor neuron-derived signaling molecule for astrocyte activation in ALS.