Mutant SOD1G93A in bone marrow-derived cells exacerbates 3-nitropropionic acid induced striatal damage in mice

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 (mSOD1G93A) 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 mSOD1G93A transgenic donor mice (WT → WT or mSODG93A → WT). After intraperitoneal injection of 3-NP, six of the eight mSOD1G93A → 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 mSOD1G93A → 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 mSOD1G93A → WT mice. Thus, the exacerbation of 3-NP-induced striatal damage in mSODG93A → WT mice was only seen after systemic administration of 3-NP, but not after intrastriatal injection. These results demonstrate that altered SOD1 activity (mSODG93A) in BMDCs affects striatal damage probably through a mechanism involving a systemic factor.