Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene.
We investigated three steps of neural precursor cell activation--proliferation, migration, and differentiation--in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.
Ohta
Yasuyuki
Y
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, Okayama, Japan. yasuyuki@cc.okayama-u.ac.jp
Nagai
Makiko
M
Nagata
Tetsuya
T
Murakami
Tetsuro
T
Nagano
Isao
I
Narai
Hisashi
H
Kurata
Tomoko
T
Shiote
Mito
M
Shoji
Mikio
M
Abe
Koji
K
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007278:Injections, Spinal / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D045442:Rotarod Performance Test / Q000379:methods; D013116:Spinal Cord / Q000473:pathology*; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics
D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D001973:Bromodeoxyuridine