TY - JOUR
T1 - Early decrease of survival signal protein and DNA repair enzyme in spinal motor neuron of presymptomatic transgenic mice with a mutant SOD1 gene
AU - Shiote, M.
AU - Ilieva, H.
AU - Nagano, I.
AU - Murakami, T.
AU - Hayashi, T.
AU - Shoji, M.
AU - Abe, K.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - We examined expressions of phosphatidylinositol 3-kinase (PI3-K), Akt and redox factor-1 protein (Ref-1) in the spinal cord of transgenic mice with G93A mutant superoxide dismutase (SOD1) (Tg), a valuable model of human amyotrophic lateral sclerosis (ALS), at early and presymptomatic stage, 18 and 25 weeks of age. Significant decrease of PI3-K, and Akt in Tg/18 mice, and of PI3-K, Akt and Ref-1 in Tg/25 was observed on immunoblotting. Immunohistochemistry revealed the significant decrease of PI3-K, Akt and Ref-1 in spinal motor neurons of Tg/25 mice. No significant loss of anterior horn neurons was detected. Therefore, the decrease of survival signal or impairment of DNA repair in the spinal motor neurons precedes a subsequent death of anterior horn neurons, and may account for the mutant SOD1-mediated motor neuronal death in this model.
AB - We examined expressions of phosphatidylinositol 3-kinase (PI3-K), Akt and redox factor-1 protein (Ref-1) in the spinal cord of transgenic mice with G93A mutant superoxide dismutase (SOD1) (Tg), a valuable model of human amyotrophic lateral sclerosis (ALS), at early and presymptomatic stage, 18 and 25 weeks of age. Significant decrease of PI3-K, and Akt in Tg/18 mice, and of PI3-K, Akt and Ref-1 in Tg/25 was observed on immunoblotting. Immunohistochemistry revealed the significant decrease of PI3-K, Akt and Ref-1 in spinal motor neurons of Tg/25 mice. No significant loss of anterior horn neurons was detected. Therefore, the decrease of survival signal or impairment of DNA repair in the spinal motor neurons precedes a subsequent death of anterior horn neurons, and may account for the mutant SOD1-mediated motor neuronal death in this model.
KW - Akt
KW - ALS
KW - Phosphatidylinositol 3-kinase
KW - Redox factor
KW - SOD1
UR - http://www.scopus.com/inward/record.url?scp=85023074449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85023074449&partnerID=8YFLogxK
U2 - 10.1016/S0531-5131(03)00069-4
DO - 10.1016/S0531-5131(03)00069-4
M3 - Article
VL - 1252
SP - 65
EP - 71
JO - International Congress Series
JF - International Congress Series
SN - 0531-5131
IS - C
ER -