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Cognitive impairment behaviors were observed by Morris water maze test, and the apoptosis of neurons was assessed by TUNEL assay. The production of neurons was analyzed by DCX and Ki67 immunohistochemistry. The expressions of CHOP and caspase\u201012 in the hippocampus were determined by Western blot and immunohistochemistry. MTX increased the expression of CHOP and caspase\u201012 and the number of TUNEL\u2010positive cells in the hippocampus by inhibiting endogenous H<jats:sub>2<\/jats:sub>S\u2010induced neuronal pyknosis in the hippocampal CA1 region. MTX decreased the number of DCX\u2010 and Ki67\u2010positive cells in the hippocampal DG region. The results of Morris water maze showed that MTX could damage the spatial memory of rats. The changes of MTX\u2010induced Morris water maze test in mice and H<jats:sub>2<\/jats:sub>S levels in serum and hippocampus, as well as the expression of CHOP and caspase\u201012 and the number of CHOP and caspase\u201012\u2010positive neurons in the hippocampus, indicated that H<jats:sub>2<\/jats:sub>S could alleviate the cognitive impairment induced by methotrexate through CHOP and caspase\u201012.<\/jats:p>","DOI":"10.1111\/fcp.12543","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T08:19:50Z","timestamp":1581149990000},"page":"559-570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Endogenous hydrogen sulfide alleviates methotrexate\u2010induced cognitive impairment by attenuating endoplasmic reticulum stress\u2010induced apoptosis via CHOP and caspase\u201012"],"prefix":"10.1111","volume":"34","author":[{"given":"Siyuan","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The National Key Clinic Specialty Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration The Engineering Technology Research Center of Education Ministry of China Zhujiang Hospital Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hematology Southern Hospital Southern Medical University Guang Zhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Movement Disorders and Neuromodulation Unit  Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-871X","authenticated-orcid":false,"given":"Li\u2010Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Pediatric Center of Zhujiang Hospital Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005903414734"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.3205"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu230"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.03.020"},{"key":"e_1_2_8_6_1","first-page":"10252","article-title":"Endoplasmic reticulum stress plays an important role in methotrexate\u2010related cognitive impairment in adult rats","volume":"10","author":"Wu L.\u2010L.","year":"2017","journal-title":"Int. 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