Restoration of microglial function by granulocyte-colony stimulating factor in ALS model mice.
We studied the effects of G-CSF on microglial reactions in mutant SOD1 (mSOD1)-Tg (G93A) ALS model mice. Following hypoglossal axotomy, the numbers of neurons and microglia expressing GDNF were significantly lower in mSOD1-Tg mice than in non-transgenic (NTG) littermates. This decrease in the number of neurons after axotomy and a decrease in the number of large myelinated axons in mSOD1-Tg mice over the disease course were improved by G-CSF, which also increased microglial recruitment. Impaired migration of cultured mSOD1-Tg microglia to MCP-1 was recovered following G-CSF treatment. Restoration of microglial responses by G-CSF may contribute to its neuroprotective effects.
Yamasaki
Ryo
R
Department of Neurology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Tanaka
Masahito
M
Fukunaga
Mami
M
Tateishi
Takahisa
T
Kikuchi
Hitoshi
H
Motomura
Kyoko
K
Matsushita
Takuya
T
Ohyagi
Yasumasa
Y
Kira
Jun-ichi
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000818:Animals; D019771:Axotomy / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D061228:Hypoglossal Nerve Injuries; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology; D020127:Recovery of Function / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D016179:Granulocyte Colony-Stimulating Factor; D000255:Adenosine Triphosphate; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase