title: Ablation of proliferating cells in the CNS exacerbates motor neuron disease caused by mutant superoxide dismutase.
abstract: Proliferation of glia and immune cells is a common pathological feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, to investigate the role of proliferating cells in motor neuron disease, SOD1(G93A) transgenic mice were treated intracerebroventicularly (i.c.v.) with the anti-mitotic drug cytosine arabinoside (Ara-C). I.c.v. delivery of Ara-C accelerated disease progression in SOD1(G93A) mouse model of ALS. Ara-C treatment caused substantial decreases in the number of microglia, NG2+ progenitors, Olig2+ cells and CD3+ T cells in the lumbar spinal cord of symptomatic SOD1(G93A) transgenic mice. Exacerbation of disease was also associated with significant alterations in the expression inflammatory molecules IL-1β, IL-6, TGF-β and the growth factor IGF-1.
authors.affiliation: Research Centre of CHUQ, Department of Psychiatry and Neurosciences, Laval University, Québec, Canada.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Audet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gowing
authors.forename: Renée
authors.initials: R
authors.lastname: Paradis
authors.forename: Geneviève
authors.initials: G
authors.lastname: Soucy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects; D016472:Motor Neuron Disease / Q000150:complications*; D013482:Superoxide Dismutase / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D003561:Cytarabine; D007334:Insulin-Like Growth Factor I; D013482:Superoxide Dismutase