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However, exposure to <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s on autophagy in neuronal cells and the effects of autophagy on <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s neurotoxicity are not clear. To answer these questions, both lipid <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s (procaine and tetracaine) and amide <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SY<\/jats:styled-content>5Y cells. Neurotoxicity was evaluated by <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content> assay, morphological alterations and median death dosage. Autophagic flux was estimated by autolysosome formation (dual fluorescence <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 assay), <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010II generation and p62 protein degradation (immunoblotting). Signalling alterations were examined by immunoblotting analysis. Inhibition of autophagy was achieved by transfection with beclin\u20101 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. We observed that <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s decreased cell viability in a dose\u2010dependent manner. The neurotoxicity of <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s was tetracaine &gt; bupivacaine &gt; ropivacaine &gt; procaine &gt; lidocaine. <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s increased autophagic flux, as reflected by increases in autolysosome formation and <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010II generation, and decrease in p62 levels. Moreover, <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s inhibited tuberin\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\/p70S6K signalling, a negative regulator of autophagy activation. Most importantly, autophagy inhibition by beclin\u20101 knockdown exacerbated the <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s\u2010provoked cell damage. Our data suggest that autophagic flux was up\u2010regulated by <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s through inhibition of tuberin\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\/p70S6K signalling, and autophagy activation served as a protective mechanism against <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s neurotoxicity. Therefore, autophagy manipulation could be an alternative therapeutic intervention to prevent <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>s\u2010induced neuronal damage.<\/jats:p>","DOI":"10.1111\/jcmm.13003","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T18:06:10Z","timestamp":1479319570000},"page":"579-587","source":"Crossref","is-referenced-by-count":31,"title":["Autophagy activated by tuberin\/<scp>mTOR<\/scp>\/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity"],"prefix":"10.1111","volume":"21","author":[{"given":"Jingwei","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyue","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital with Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics First Affiliated Hospital with Nanjing Medical University Nanjing 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