Parvalbumin and calbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene.
Immunohistochemical study was performed to examine if calcium-binding proteins are involved in the degeneration of motor neurons in the brain stems and the spinal cords of transgenic mice carrying a G93A mutant human SOD1 gene. Specimens from age-matched non-transgenic wild-type mice served as controls. In the spinal cord of the controls, the density of parvalbumin-immunoreactive neurons was highest in the large anterior horn neurons and lower in the posterior horn neurons in the spinal cord. On the other hand, calbindin D-28k immunoreactivity was much less apparent than that observed with parvalbumin antisera. Rexed's lamina II was densely immunostained for calbindin D-28k, whereas, in the anterior horn, calbindin-D-28k-positive small neurons were barely dispersed in a scattered pattern. In transgenic mice, parvalbumin-positive anterior horn neurons were severely reduced, even at the presymptomatic stage, whereas calbindin-positive neurons were largely preserved. At the symptomatic stage, both parvalbumin and calbindin D-28k immunoreactivity markedly diminished or disappeared in the anterior horn. Immunoblotting analysis revealed a significant reduction of immunoreactivity to parvalbumin antibody in transgenic mice compared with the controls. In the brain stem, parvalbumin-positive oculomotor and abducens neurons and the calbindin D-28k-positive sixth nucleus were well-preserved in transgenic mice as well as in the controls. Thus, the diffuse and severe loss of parvalbumin immunoreactivity of large motor neurons even at early stages in SOD1-transgenic mice and the absence of calbindin D-28k immunoreactivity of normal large motor neurons suggest that these calcium-binding proteins may contribute to selective vulnerability and an early loss of function of large motor neurons in this SOD1-transgenic mouse model.
Sasaki
Shoichi
S
Department of Neurology, Neurological Institute, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. ssasaki@nij.twmu.ac.jp
Warita
Hitoshi
H
Komori
Takashi
T
Murakami
Tetsuro
T
Abe
Koji
K
Iwata
Makoto
M
D000010:Abducens Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D064026:Calbindins; D048429:Cell Size; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009802:Oculomotor Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010320:Parvalbumins / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase