title: Mutant SOD1G93A in bone marrow-derived cells exacerbates 3-nitropropionic acid induced striatal damage in mice.
abstract: 3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, produces selective lesions in striatal neurons that resemble those observed in Huntington's disease neuropathology. In this study, we evaluated the role of peripheral bone marrow-derived cells (BMDCs) in the 3-NP-induced striatal damage by transplanting bone marrow cells with human SOD1 G93A mutation (mSOD1(G93A)) which induces amyotrophic lateral sclerosis through an unknown gain of toxicity and mitochondrial dysfunction. We assessed striatal damage after 3-NP treatment in the recipient C57BL/6 wild-type (WT) mice that received bone marrow cells from WT or mSOD1(G93A) transgenic donor mice (WT-->WT or mSOD(G93A)-->WT). After intraperitoneal injection of 3-NP, six of the eight mSOD1(G93A)-->WT mice had bilateral striatal lesions while only one out of eight WT-->WT mice had a striatal lesion. The lesion volume was significantly higher in the mSOD1(G93A)-->WT mice than in the WT-->WT mice. However, following an intrastriatal injection of 3-NP, there was no significant difference in the lesion volumes between the WT-->WT mice and mSOD1(G93A)-->WT mice. Thus, the exacerbation of 3-NP-induced striatal damage in mSOD(G93A)-->WT mice was only seen after systemic administration of 3-NP, but not after intrastriatal injection. These results demonstrate that altered SOD1 activity (mSOD(G93A)) in BMDCs affects striatal damage probably through a mechanism involving a systemic factor.
authors.affiliation: Department of Neurology, Boston University School of Medicine, 715 Albany Street, E301 Boston, MA, USA.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Huang
authors.forename: Liqun
authors.initials: L
authors.lastname: Yu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology; D016026:Bone Marrow Transplantation; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D007274:Injections, Intraperitoneal / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D009498:Neurotoxins; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000235:genetics; D011422:Propionates / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D018183:Transplantation Chimera
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C015392:3-nitropropionic acid