title: Region-specific changes in the immunoreactivity of SIRT1 expression in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.
abstract: SIRT1, which is a mammalian homolog of yeast nicotinamide adenine dinucleotide-dependent deacetylase silent information regulator 2 (SIR2), is the best-characterized SIRT family member. SIRT1 regulates longevity in several model organisms and is involved in several processes in mammalian cells, including cell survival, differentiation, and metabolism. In the present study, we used SOD1(G93A) mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies, RT-PCR and western blotting analysis in order to investigate the changes of SIRT1 immunoreactivity in the central nervous system of these mice. An increased expression of SIRT1 was obvious in the cerebral cortex, hippocampal formation, thalamus and spinal cord of symptomatic SOD1(G93A) transgenic mice. In the cerebral cortex, SIRT1 immunoreactivity was significantly increased in pyramidal cells of SOD1(G93A) transgenic mice. In the hippocampal formation of these mice, SIRT1 immunoreactivity was increased in the pyramidal cells of the CA1-3 areas and in the granule cells of the dentate gyrus. In addition, SIRT1 immunoreactivity was increased in the spinal cord and thalamus of symptomatic SOD1(G93A) transgenic mice. This study, which showed increased SIRT1 in different brain regions of SOD1(G93A) transgenic mice, may provide clues to the understanding of selective neuronal loss in ALS. These findings suggest a role for SIRT1 in the motor functions in ALS but the mechanisms and functional implications of increased SIRT1 require elucidation.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Shin
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Park
authors.forename: Gwon Sik
authors.initials: GS
authors.lastname: Kim
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Choong Ik
authors.initials: CI
authors.lastname: Cha
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D056564:Sirtuin 1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1