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To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24\u00a0hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome\u2010related signals, imbalanced oxidative stress\/anti\u2010oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>\u00a0mol\/L) was used to pre\u2010treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis\u2010induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase\/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase\u20103\u03b2 and nuclear factor\u2010\u03baB signals, ER stress and Golgi stress, and the abnormal autophagy\u2010lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis\u2010induced injuries.<\/jats:p>","DOI":"10.1111\/jcmm.15351","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T14:55:10Z","timestamp":1588604110000},"page":"6928-6942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Protection of melatonin against acidosis\u2010induced neuronal injuries"],"prefix":"10.1111","volume":"24","author":[{"given":"Yan","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Key Laboratory of Neurological Disease of National Education Ministry Institute for Brain Research Huazhong University of Science and Technology Wuhan China"},{"name":"School of Medicine Hunan Normal University Changsha 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