{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:16:33Z","timestamp":1767903393831,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,2,23]],"date-time":"2001-02-23T00:00:00Z","timestamp":982886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2001,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mechanisms of neuronal degeneration in motor neuron disease are not fully understood. We tested the hypothesis that oxidative stress in vitro and axotomy in vivo induce single\u2010strand breaks (SSB) in DNA, a form of early DNA damage, in adult motor neurons early during their degeneration. We developed and characterized a novel cell suspension system enriched in motor neurons from adult rat spinal cord ventral horn. This cell system is \u223c84% neurons, with \u223c86% of these neurons being motor neurons; \u223c72% of these motor neurons are \u03b1\u2010motor neurons. Motor neuron viability in suspension is \u223c100% immediately after isolation and \u223c61% after 12 hours of incubation. During incubation, isolated motor neurons generate high levels of superoxide. We used single\u2010cell gel electrophoresis (comet assay) to detect DNA\u2010SSB in motor neurons. Exposure of motor neurons to nitric oxide (NO) donors (sodium nitroprusside or NONOate), H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, or NO donor plus H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> rapidly induces DNA\u2010SSB and causes motor neuron degeneration, the occurrence of which is dose and time related, as represented by comet formation and cell loss. Motor neuron toxicity is potentiated by cotreatment with NO donor and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> (at nontoxic concentrations alone). Peroxynitrite causes DNA\u2010SSB in motor neurons. The DNA damage profiles (shown by the comet morphology and moment) of NO donors, NO donor plus H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, and peroxynitrite are similar. In an in vivo model of motor neuron apoptosis, DNA\u2010SSB accumulate slowly in avulsed motor neurons before apoptotic nuclear features emerge, and the comet fingerprint is similar to NO toxicity. We conclude that motor neurons challenged by oxidative stress and axotomy accumulate DNA\u2010SSB early in their degeneration and that the formation of peroxynitrite is involved in the mechanisms. J. Comp. Neurol. 432:35\u201360, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.1087","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T18:02:53Z","timestamp":1030298573000},"page":"35-60","source":"Crossref","is-referenced-by-count":50,"title":["Motor neurons rapidly accumulate DNA single\u2010strand breaks after in vitro exposure to nitric oxide and peroxynitrite and in vivo axotomy"],"prefix":"10.1002","volume":"432","author":[{"given":"Zhiping","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,2,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/364584a0","article-title":"ALS, SOD and peroxynitrite","volume":"364","author":"Beckman 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