{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:25:37Z","timestamp":1790673937166,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["BMBF 20150065"],"award-info":[{"award-number":["BMBF 20150065"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["57514679"],"award-info":[{"award-number":["57514679"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012655","name":"Universidad de Antofagasta","doi-asserted-by":"publisher","award":["ANT 1855"],"award-info":[{"award-number":["ANT 1855"]}],"id":[{"id":"10.13039\/501100012655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012655","name":"Universidad de Antofagasta","doi-asserted-by":"publisher","award":["SEM18\u201004"],"award-info":[{"award-number":["SEM18\u201004"]}],"id":[{"id":"10.13039\/501100012655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008992","name":"International Society for Neurochemistry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008992","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Autism spectrum disorder (ASD) is a heterogeneous neurodevelopment disorder resulting from different etiological factors, both genetic and\/or environmental. These factors can lead to abnormal neuronal development on dendrite and synaptic function at the central nervous system. Recent studies have shown that a subset of ASD patients display increased circulation levels of the tyrosine metabolite, <jats:italic>p<\/jats:italic>\u2010cresol, related to chronic intestinal disorders because of dysbiosis of the intestinal microbiota. In particular, abnormal presence of intestinal <jats:italic>Clostridium sp<\/jats:italic>. has been linked to high levels of <jats:italic>p<\/jats:italic>\u2010cresol in ASD children younger than 8\u00a0years. However, the role of <jats:italic>p<\/jats:italic>\u2010cresol during development of the central nervous system is unknown. Here, we evaluated in vitro the effect of <jats:italic>p<\/jats:italic>\u2010cresol on neurite outgrowth in N2a and PC12 cell lines and dendritic morphology, synaptic density, neuronal activity, and calcium responses in primary rat hippocampal neurons. <jats:italic>p<\/jats:italic>\u2010cresol inhibits neural differentiation and neurites outgrowth in N2a and PC12 neuronal cell lines. In hippocampal neuronal cultures, Sholl's analysis shows a decrease in the dendritic arborization of neurons treated with <jats:italic>p<\/jats:italic>\u2010cresol. Synaptic density analyzed with the synaptic markers Piccolo and Shank2 is diminished in hippocampal neurons treated with <jats:italic>p<\/jats:italic>\u2010cresol. Electrically evoked intracellular calcium rise was drastically, but reversely, blocked by <jats:italic>p<\/jats:italic>\u2010cresol, whereas that spontaneous neuronal activity was severely affected by early addition of the metabolite. These findings show that <jats:italic>p<\/jats:italic>\u2010cresol alters dendrite development, synaptogenesis, and synapse function of neurons in culture, therefore, neuronal alterations occurring in ASD children may be related to this metabolite and dysbiosis of the intestinal microbiota.\n<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><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\/jnc15604-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15604","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T09:41:28Z","timestamp":1646732488000},"page":"335-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The metabolite <scp><i>p<\/i><\/scp>\u2010cresol impairs dendritic development, synaptogenesis, and synapse function in hippocampal neurons: Implications for autism spectrum disorder"],"prefix":"10.1111","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-6177","authenticated-orcid":false,"given":"Sheyla","family":"Guzm\u00e1n\u2010Salas","sequence":"first","affiliation":[{"name":"Departamento Biom\u00e9dico Universidad de Antofagasta  Antofagasta Chile"},{"name":"Centre for Biotechnology and Bioengineering CeBiB  Antofagasta Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Weber","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Neurobiology  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Malci","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Neurobiology  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Neurobiology  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Herrera\u2010Molina","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Neurobiology  Magdeburg Germany"},{"name":"Centro Integrativo de Biolog\u00eda y Qu\u00edmica Aplicada, Universidad Bernardo O'Higgins  Santiago Chile"},{"name":"Center for Behavioral Brain Sciences and Medical Faculty Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-0144","authenticated-orcid":false,"given":"Waldo","family":"Cerpa","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n y Patolog\u00eda Neuronal; Departamento de Biolog\u00eda Celular y Molecular, Facultad de Ciencias Biol\u00f3gicas Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"},{"name":"Centro de Excelencia en Biomedicina de Magallanes (CEBIMA); Universidad de Magallanes  Punta Arenas Chile"},{"name":"Centro de Envejecimiento y Regeneraci\u00f3n (CARE); Departamento de Biolog\u00eda Celular y Molecular, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Dorador","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology and Bioengineering CeBiB  Antofagasta Chile"},{"name":"Instituto Antofagasta, Universidad de Antofagasta  Antofagasta Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-2690","authenticated-orcid":false,"given":"Janetti","family":"Signorelli","sequence":"additional","affiliation":[{"name":"Departamento Biom\u00e9dico Universidad de Antofagasta  Antofagasta Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-5880","authenticated-orcid":false,"given":"Pedro","family":"Zamorano","sequence":"additional","affiliation":[{"name":"Departamento Biom\u00e9dico Universidad de Antofagasta  Antofagasta Chile"},{"name":"Instituto Antofagasta, Universidad de Antofagasta  Antofagasta Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596.dsm18"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.01.065"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2018.1534514"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(09)70139-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2010.548010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.04.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.03.018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.589"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14527"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldy026"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH03\u201007\u20100491"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010013\u20101973\u2010x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114446"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959\u20104388(00)00182\u20103"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.04.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.03.010"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2004.02.006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208494"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030521"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3125"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2010.06.008"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/341914"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2014.936911"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13442"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2015.00019"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2019.1555468"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1854"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.024"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971020)387:2<167::AID-CNE1>3.0.CO;2-Z"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.356"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201042183\u20100"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010016\u20100225\u20107"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2017.12.007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030613"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010100913\u2010013020"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010018\u20101378\u20100"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010publhealth\u2010031816\u2010044318"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6904a1"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.274076"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10040233"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2741"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2012.09.002"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.10.038"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2004.05.010"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1515\/bc.2005.114"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010017\u20100242\u20101"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186687"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.10135"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000647"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748\u20101716.2007.01805.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11208"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ\u201011\u20100046"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010019\u20100365\u20108"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.15604","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:46:59Z","timestamp":1692982019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/jnc.15604"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15604","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]},"assertion":[{"value":"2021-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}