TY - JOUR
T1 - Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model
AU - Shibata, Noriyuki
AU - Kawaguchi, Motoko
AU - Uchida, Koji
AU - Kakita, Akiyoshi
AU - Takahashi, Hitoshi
AU - Nakano, Ryoichi
AU - Fujimura, Harutoshi
AU - Sakoda, Saburo
AU - Ihara, Yuetsu
AU - Nobukuni, Keigo
AU - Takehisa, Yasushi
AU - Kuroda, Shigetoshi
AU - Kokubo, Yasumasa
AU - Kuzuhara, Shigeki
AU - Honma, Taku
AU - Mochizuki, Yoko
AU - Mizutani, Tomohiko
AU - Yamada, Satoshi
AU - Toi, Sono
AU - Sasaki, Shoichi
AU - Iwata, Makoto
AU - Hirano, Asao
AU - Yamamoto, Tomoko
AU - Kato, Yoichiro
AU - Sawada, Tatsuo
AU - Kobayashi, Makio
PY - 2007/2
Y1 - 2007/2
N2 - Growing evidence documents oxidative stress involvement in ALS. We previously demonstrated accumulation of a protein-bound form of the highly toxic lipid peroxidation product crotonaldehyde (CRA) in the spinal cord of sporadic ALS patients. In the present study, to the determine the role for CRA in the disease processes of superoxide dismutase-1 (SOD1) mutation-associated familial ALS (FALS), we performed immunohistochemical and semiquantitative cell count analyses of protein-bound CRA (P-CRA) in the spinal cord of SOD1-mutated FALS and its transgenic mouse model. Immunohistochemical analysis revealed increased P-CRA immunoreactivity in the spinal cord of the FALS patients and the transgenic mice compared to their respective controls. In the FALS patients, P-CRA immunoreactivity was localized in almost all of the chromatolytic motor neurons, neurofilamentous conglomerates, spheroids, cordlike swollen axons, reactive astrocytes and microglia, and the surrounding neuropil in the affected areas represented by the anterior horns. In the transgenic mice, P-CRA immunoreactivity was localized in only a few ventral horn glia in the presymptomatic stage, in almost all of the vacuolated motor neurons and cordlike swollen axons and some of the ventral horn reactive astrocytes and microglia in the onset stage, and in many of the ventral horn reactive astrocytes and microglia in the advanced stage. Cell count analysis on mouse spinal cord sections disclosed a statistically significant increase in the density of P-CRA-immunoreactive glia in the ventral horns of the young to old G93A mice compared to the age-matched control mice. The present results indicate that enhanced CRA formation occurs in motor neurons and reactive glia in the spinal cord of SOD1-mutated FALS and its transgenic mouse model as well as sporadic ALS, suggesting implications for CRA in the pathomechanism common to these forms of ALS.
AB - Growing evidence documents oxidative stress involvement in ALS. We previously demonstrated accumulation of a protein-bound form of the highly toxic lipid peroxidation product crotonaldehyde (CRA) in the spinal cord of sporadic ALS patients. In the present study, to the determine the role for CRA in the disease processes of superoxide dismutase-1 (SOD1) mutation-associated familial ALS (FALS), we performed immunohistochemical and semiquantitative cell count analyses of protein-bound CRA (P-CRA) in the spinal cord of SOD1-mutated FALS and its transgenic mouse model. Immunohistochemical analysis revealed increased P-CRA immunoreactivity in the spinal cord of the FALS patients and the transgenic mice compared to their respective controls. In the FALS patients, P-CRA immunoreactivity was localized in almost all of the chromatolytic motor neurons, neurofilamentous conglomerates, spheroids, cordlike swollen axons, reactive astrocytes and microglia, and the surrounding neuropil in the affected areas represented by the anterior horns. In the transgenic mice, P-CRA immunoreactivity was localized in only a few ventral horn glia in the presymptomatic stage, in almost all of the vacuolated motor neurons and cordlike swollen axons and some of the ventral horn reactive astrocytes and microglia in the onset stage, and in many of the ventral horn reactive astrocytes and microglia in the advanced stage. Cell count analysis on mouse spinal cord sections disclosed a statistically significant increase in the density of P-CRA-immunoreactive glia in the ventral horns of the young to old G93A mice compared to the age-matched control mice. The present results indicate that enhanced CRA formation occurs in motor neurons and reactive glia in the spinal cord of SOD1-mutated FALS and its transgenic mouse model as well as sporadic ALS, suggesting implications for CRA in the pathomechanism common to these forms of ALS.
KW - Amyotrophic lateral sclerosis
KW - Crotonaldehyde
KW - Lipid peroxidation
KW - Superoxide dismutase-1
KW - Transgenic mouse model
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UR - http://www.scopus.com/inward/citedby.url?scp=33846430885&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1789.2006.00746.x
DO - 10.1111/j.1440-1789.2006.00746.x
M3 - Article
C2 - 17319283
AN - SCOPUS:33846430885
SN - 0919-6544
VL - 27
SP - 49
EP - 61
JO - Neuropathology
JF - Neuropathology
IS - 1
ER -