title: Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis.
abstract: The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons isolated from autopsied patients with sporadic ALS were examined. Gene expression was quantitatively assessed by real-time reverse transcription polymerase chain reaction and in situ hybridization. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were downregulated, and 1% were upregulated in motor neurons. Downregulated genes included those associated with cytoskeleton/axonal transport, transcription, and cell surface antigens/receptors, such as dynactin, microtubule-associated proteins, and early growth response 3 (EGR3). In contrast, cell death-associated genes were mostly upregulated. Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated. Moreover, neuroprotective neurotrophic factors such as ciliary neurotrophic factor (CNTF), Hepatocyte growth factor (HGF), and glial cell line-derived neurotrophic factor were upregulated. Inflammation-related genes, such as those belonging to the cytokine family, were not, however, significantly upregulated in either motor neurons or ventral horns. The motor neuron-specific gene expression profile in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death and are helpful for developing new therapeutic strategies.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Jiang
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Yideng
authors.initials: Y
authors.lastname: Liang
authors.forename: Shinichi
authors.initials: S
authors.lastname: Terao
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ishigaki
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Niwa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Manabu
authors.initials: M
authors.lastname: Doyu
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D000870:Anterior Horn Cells / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007834:Lasers; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D017931:DNA Primers