{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:43Z","timestamp":1790874523703,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,6,3]],"date-time":"2007-06-03T00:00:00Z","timestamp":1180828800000},"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":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a major co\u2010morbidity of Parkinson\u2019s disease (PD), depression is associated with the loss of serotonergic neurons. Our recent study has shown that midbrain dopaminergic neurons are particularly vulnerable to microtubule\u2010depolymerizing agents including rotenone, an environmental toxin linked to PD. Here we show that rotenone also selectively killed serotonergic neurons in midbrain neuronal cultures. Its selective toxicity was significantly decreased by the microtubule\u2010stabilizing drug taxol and mimicked by microtubule\u2010depolymerizing agents such as colchicine and nocodazole. Microtubule depolymerization induced by rotenone or colchicine caused vesicle accumulation in the soma and killed serotonergic neurons through a mechanism dependent on serotonin metabolism in the cytosol. Blocking serotonin synthesis or degradation, as well as application of antioxidants, significantly reduced the selective toxicity of rotenone or colchicine. Inhibition of vesicular sequestration of serotonin exerted a selective toxicity on serotonergic neurons that was mitigated by blocking serotonin metabolism. Over\u2010expression of parkin, a protein\u2010ubiquitin E3 ligase that strongly binds to microtubules, greatly attenuated the selective toxicity of rotenone or colchicine. The protective effects of parkin were abrogated by its PD\u2010linked mutations. Together, our results suggest that rotenone and parkin affect the survival of serotonergic neurons by impacting on microtubules in opposing manners.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04741.x","type":"journal-article","created":{"date-parts":[[2007,6,22]],"date-time":"2007-06-22T20:02:23Z","timestamp":1182542543000},"page":"303-311","source":"Crossref","is-referenced-by-count":51,"title":["Rotenone selectively kills serotonergic neurons through a microtubule\u2010dependent mechanism"],"prefix":"10.1111","volume":"103","author":[{"given":"Yong","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,6,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/81834"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(74)90210-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.3.1049"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84014-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530270125028"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.5.1583"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/089198879000300102"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858406293853"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/009841098158872"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1739-1748.2004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706X(94)90066-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(02)00098-0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(97)01168-9"},{"key":"e_1_2_7_16_1","first-page":"13","article-title":"Diminished subcortical nuclei volumes in Parkinson\u2019s disease by MR imaging","volume":"40","author":"Lisanby S. 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