Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis.
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.
Jiang
Yue-Mei
YM
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yamamoto
Masahiko
M
Kobayashi
Yasushi
Y
Yoshihara
Tsuyoshi
T
Liang
Yideng
Y
Terao
Shinichi
S
Takeuchi
Hideyuki
H
Ishigaki
Shinsuke
S
Katsuno
Masahisa
M
Adachi
Hiroaki
H
Niwa
Jun-ichi
J
Tanaka
Fumiaki
F
Doyu
Manabu
M
Yoshida
Mari
M
Hashizume
Yoshio
Y
Sobue
Gen
G
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*
D017931:DNA Primers