Pre-symptomatic alterations in subcellular betaCGRP 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 alphaCGRP and betaCGRP gene expression and alphaCGRP immunoreactivity remained unaltered throughout disease, and alphaCGRP gene deficiency had no effect on disease progression. In contrast, betaCGRP 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 betaCGRP-containing dysmorphic dendritic structures with processes of activated astrocytes, in combination with a selective expression of the CGRP receptor by astrocytes, suggests that betaCGRP may function as a motor neuron-derived signaling molecule for astrocyte activation in ALS.
Ringer
Cornelia
C
Department of Molecular Neurosciences, Institute of Anatomy and Cell Biology, Philipps-University, Robert-Koch-Strabetae 8, Marburg D-35032, Germany.
Weihe
Eberhard
E
Schütz
Burkhard
B
D000375:Aging; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D001369:Axons / Q000473:pathology / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005911:Gliosis / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015740:Calcitonin Gene-Related Peptide