Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.
Familial amyotrophic lateral sclerosis (FALS)-linked mutations in copper-zinc superoxide dismutase (SOD1) cause motor neuron death through one or more acquired toxic properties. We analyzed the molecular mechanism underlying motor neuron degeneration in the transgenic mouse model expressing the SOD1 gene with G93A mutation. Using cDNA microarray, the differentially expressed genes were identified in the spinal cords of G93A mice, 30 being elevated and seven decreased. cDNA microarray analysis to monitor gene expression during neurodegeneration revealed an up-regulation of genes related to an inflammatory process, such as the tumor necrosis factor-alpha (TNF-alpha) gene, resulting from glial cell activation, together with the change in apoptosis-related gene expression, such as caspase-1. The increased expression of the inflammation- and apoptosis-related genes occurred at 11 weeks of age in the presymptomatic stage prior to motor neuron death. These results suggest a mechanism of neurodegeneration that includes an inflammatory response as an important component. Thus, ALS has paralleled other neurodegenerative disorders, such as Alzheimer's and prion diseases, in which the inflammatory process is believed to participate directly in neuronal death.
Yoshihara
Tsuyoshi
T
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ishigaki
Shinsuke
S
Yamamoto
Masahiko
M
Liang
Yideng
Y
Niwa
Jun-ichi
J
Takeuchi
Hideyuki
H
Doyu
Manabu
M
Sobue
Gen
G
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
D012333:RNA, Messenger; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1