{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:14:15Z","timestamp":1788786855262,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstc2021jcyj\u2010msxmX0065"],"award-info":[{"award-number":["cstc2021jcyj\u2010msxmX0065"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neuroinflammation and microglial activation\u2010related dendritic injury contribute to the pathogenesis of Autism Spectrum Disorder (ASD). Previous studies show that Progranulin (PGRN) is a growth factor associated with inflammation and synaptic development, but the role of PGRN in autism and the mechanisms underlying changes in PGRN expression remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the impact of PGRN in autism, we stereotactically injected recombinant PGRN into the hippocampus of ASD model rats. Additionally, we explored the possibility that sortilin may be the factor behind the alterations in PGRN by utilizing <jats:italic>SORT1<\/jats:italic> knockdown. Ultimately, we aimed to identify potential targets for the treatment of autism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PGRN could alleviate inflammatory responses, protect neuronal dendritic spines, and ameliorate autism\u2010like behaviors. Meanwhile, elevated expression of sortilin and decreased levels of PGRN were observed in both ASD patients and rats. Enhanced sortilin levels facilitated PGRN internalization into lysosomes. Notably, suppressing <jats:italic>SORT1<\/jats:italic> expression amplified PGRN levels, lessened microglial activation, and mitigated inflammation, thereby alleviating autism\u2010like behaviors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, our findings highlight elevated sortilin levels in ASD rat brains, exacerbating dendrite impairment by affecting PGRN expression. PGRN supplementation and <jats:italic>SORT1<\/jats:italic> knockdown hold potential as therapeutic strategies for ASD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70015","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T02:39:28Z","timestamp":1725244768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sortilin is associated with progranulin deficiency and autism\u2010like behaviors in valproic acid\u2010induced autism rats"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8573-6958","authenticated-orcid":false,"given":"Ailing","family":"Liao","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health Chongqing Population and Family Planning Science and Technology Research Institute  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Science Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shali","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashi","family":"Wang","sequence":"additional","affiliation":[{"name":"Library\/Archive Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Science Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Science Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.23661"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-020-04685-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247190"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20315"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-012-1513-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.05.024"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104286"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2023.114384"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104918"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202301957"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh0609"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209954"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852919001603"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0334-7"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1861-8"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22430"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-010-0067-1"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23091"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199214"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.01.003"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2019.06.006"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604992113"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.034"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021023"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt534"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01507"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_30_1","volume-title":"Recognition and Alleviation of Pain and Distress in Laboratory Animals","author":"Animals CoRaAoPiL","year":"2009"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1258\/0023677011911660"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3791\/57648"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-4"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.09.005"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.08.036"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63113"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24175"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah5642"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700477114"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15375"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220000"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.041"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-020-00349-y"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202004107"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02645-1"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2663-16.2018"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146569"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1125428"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0681-0"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02705-6"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030230"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00395"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201502029"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-33"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab310"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1590"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235866"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.01.027"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/eneuro.0100-17.2017"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.586107"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/abt\/tbac028"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.002"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566523217666170510155803"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T03:56:57Z","timestamp":1727755017000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/cns.70015"],"URL":"https:\/\/doi.org\/10.1111\/cns.70015","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2023-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70015"}}