{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:08:56Z","timestamp":1762520936144},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,9,27]],"date-time":"2004-09-27T00:00:00Z","timestamp":1096243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dysregulated stimulation of microglia, the resident macrophages in the brain, can lead to excessive induction of inflammatory agents and subsequently damage to neurons. Fibrillar \u03b2\u2010amyloid peptide (fA\u03b2), a major component of senile plaques in Alzheimer's disease (AD) brain, is known to induce microglial\u2010mediated neurotoxicity under certain conditions. Microglial \u2018priming\u2019 by macrophage colony stimulatory factor (MCSF) or interferon\u2010gamma (IFN\u03b3) appears to be required for this fA\u03b2\u2010induced microglia mediated neurotoxicity <jats:italic>in vitro<\/jats:italic>. We report here that while both MCSF and IFN\u03b3 induce microglial\u2010mediated fA\u03b2 neurotoxicity, their mechanisms of toxicity differ. The enhancement of neurotoxicity by IFN\u03b3 or MCSF is not due to enhanced A\u03b2 ingestion by microglia or to the direct effect of proinflammatory cytokine production. The neurotoxicity resulting from IFN\u03b3\/fA\u03b2 treatment was blocked by pretreatment with nitric oxide synthase inhibitor <jats:sc>l<\/jats:sc>\u2010<jats:italic>N\u2010<\/jats:italic>5\u2010(1\u2010iminoethyl) ornithine hydrochloride (<jats:sc>l<\/jats:sc>\u2010NIO), consistent with a role for nitric oxide in the IFN\u03b3\u2010mediated toxicity mechanism. In contrast, no induction of nitric oxide production was detected for microglia treated with MCSF\/fA\u03b2. Furthermore, inhibiting the generation of reactive oxygen species (ROS) using the specific NADPH oxidase inhibitor apocynin reversed fA\u03b2\/MCSF\u2010induced neurotoxicity while <jats:sc>l<\/jats:sc>\u2010NIO had little effect. As MCSF is endogenously expressed within the brain, and both its level and that of the MCSF receptor are dramatically increased in the AD brain, the neurotoxicity resulting from ROS release by fA\u03b2\/MCSF coactivated microglia may be a more appropriate model for assessing fA\u03b2\u2010induced microglial\u2010mediated neuropathology in AD.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02765.x","type":"journal-article","created":{"date-parts":[[2004,10,15]],"date-time":"2004-10-15T08:59:32Z","timestamp":1097830772000},"page":"623-633","source":"Crossref","is-referenced-by-count":30,"title":["Macrophage colony stimulatory factor and interferon\u2010\u03b3 trigger distinct mechanisms for augmentation of \u03b2\u2010amyloid\u2010induced microglia\u2010mediated neurotoxicity"],"prefix":"10.1111","volume":"91","author":[{"given":"M.","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Pisalyaput","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Galvan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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