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TD\u2010induced brain damage is used to model neurodegenerative disorders, and the mechanism for the neuronal death is still unclear. We hypothesized that autophagy might be activated in the TD brain and play a protective role in TD\u2010induced neuronal death. Our results demonstrated that TD induced the accumulation of autophagosomes in thalamic neurons measured by transmission electron microscopy, and the up\u2010regulation of autophagic markers LC3\u2010II, Atg5, and Beclin1 as measured with western blotting. TD also increased the expression of autophagic markers and induced LC3 puncta in SH\u2010SY5Y neuroblastoma cells. TD\u2010induced expression of autophagic markers was reversed once thiamine was re\u2010administered. Both inhibition of autophagy by wortmannin and Beclin1 siRNA potentiated TD\u2010induced death of SH\u2010SY5Y cells. In contrast, activation of autophagy by rapamycin alleviated cell death induced by TD. Intraperitoneal injection of rapamycin stimulated neuronal autophagy and attenuated TD\u2010induced neuronal death and microglia activation in the submedial thalamus nucleus (SmTN). TD inhibited the phosphorylation of p70S6 kinase, suggesting <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\/p70S6 kinase pathway was involved in the TD\u2010induced autophagy. These results suggest that autophagy is neuroprotective in response to TD\u2010induced neuronal death in the central nervous system. This opens a potential therapeutic avenue for neurodegenerative diseases caused by mild impairment of oxidative metabolism.<\/jats:p><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12268-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Autophagy is neuroprotective in response to thiamine deficiency (TD)\u2010induced neuronal death. TD caused neuronal damage and induced the formation of autophagosome, and increased the expression of autophagy\u2010related proteins. Autophagy sequestered damaged and dysfunctional organelles\/protein, and transported them to lysosomes for degradation\/recycling. This process provided nutrients for injured neurons. Wortmannin and knockdown of Beclin1 inhibited autophagy, and exacerbated TD\u2010induced cell death, while activation of autophagy by rapamycin offered protection against TD neurotoxicity.<\/jats:p>","DOI":"10.1111\/jnc.12268","type":"journal-article","created":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T16:23:50Z","timestamp":1366043030000},"page":"805-818","source":"Crossref","is-referenced-by-count":32,"title":["Autophagy alleviates neurodegeneration caused by mild impairment of oxidative metabolism"],"prefix":"10.1111","volume":"126","author":[{"given":"Ya","family":"Meng","sequence":"first","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifen","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology University of Kentucky College of Medicine Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zun\u2010Ji","family":"Ke","sequence":"additional","affiliation":[{"name":"Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,9]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"25","article-title":"Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease","volume":"12","author":"Anglade P.","year":"1997","journal-title":"Histol. 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