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However, there is only limited information concerning its underlying mechanism and therapeutic strategy. Here, we investigated the effects of\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>gondii<\/jats:italic>\n                      chronic infection on the goal-directed cognitive behavior in mice. Moreover, we evaluated the preventive and therapeutic effect of dimethyl itaconate on the behavior deficits induced by the parasite.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The infection model was established by orally infecting the cysts of\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>gondii<\/jats:italic>\n                      . Dimethyl itaconate was intraperitoneally administered before or after the infection. Y-maze and temporal order memory (TOM) tests were used to evaluate the prefrontal cortex-dependent behavior performance. Golgi staining, transmission electron microscopy, indirect immunofluorescence, western blot, and RNA sequencing were utilized to determine the pathological changes in the prefrontal cortex of mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We showed that\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>gondii<\/jats:italic>\n                      infection impaired the prefrontal cortex-dependent goal-directed behavior. The infection significantly downregulated the expression of the genes associated with synaptic transmission, plasticity, and cognitive behavior in the prefrontal cortex of mice. On the contrary, the infection robustly upregulated the expression of activation makers of microglia and astrocytes. In addition, the metabolic phenotype of the prefrontal cortex post infection was characterized by the enhancement of glycolysis and fatty acid oxidation, the blockage of the Krebs cycle, and the disorder of aconitate decarboxylase 1 (ACOD1)-itaconate axis. Notably, the administration of dimethyl itaconate significantly prevented and treated the cognitive impairment induced by\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>gondii<\/jats:italic>\n                      , which was evidenced by the improvement of behavioral deficits, synaptic ultrastructure lesion and neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The present study demonstrates that\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>gondii<\/jats:italic>\n                      infection induces the deficits of the goal-directed behavior, which is associated with neuroinflammation, the impairment of synaptic ultrastructure, and the metabolic shifts in the prefrontal cortex of mice. Moreover, we report that dimethyl itaconate has the potential to prevent and treat the behavior deficits.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0011350","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T13:52:12Z","timestamp":1685541132000},"page":"e0011350","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Dimethyl itaconate ameliorates the deficits of goal-directed behavior in Toxoplasma gondii infected mice"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-6938","authenticated-orcid":true,"given":"Yongshuai","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rundong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuanzhuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2641-1759","authenticated-orcid":true,"given":"Wei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"pntd.0011350.ref001","author":"AD international.org","year":"2018"},{"issue":"4","key":"pntd.0011350.ref002","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jalz.2017.12.006","article-title":"The cost of Alzheimer\u2019s disease in China and re-estimation of costs worldwide.","volume":"14","author":"J Jia","year":"2018","journal-title":"Alzheimers Dement."},{"issue":"4","key":"pntd.0011350.ref003","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/alzrt269","article-title":"Alzheimer\u2019s disease drug-development pipeline: few candidates, frequent failures","volume":"6","author":"JL Cummings","year":"2014","journal-title":"Alzheimers Res Ther"},{"issue":"9425","key":"pntd.0011350.ref004","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis.","volume":"363","author":"JG Montoya","year":"2004","journal-title":"Lancet"},{"key":"pntd.0011350.ref005","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejogrb.2020.10.003","article-title":"Toxoplasmosis in pregnancy.","volume":"255","author":"M Ahmed","year":"2020","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"pntd.0011350.ref006","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/schbul\/sbm008","article-title":"Effects of Toxoplasma gondii infection on the brain","volume":"33","author":"VB Carruthers","year":"2007","journal-title":"Schizophr Bull"},{"issue":"8","key":"pntd.0011350.ref007","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/trstmh\/trz025","article-title":"An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy","volume":"113","author":"M Sadeghi","year":"2019","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0011350.ref008","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.actatropica.2019.05.015","article-title":"Toxoplasma gondii infection and risk of Parkinson and Alzheimer diseases: A systematic review and meta-analysis on observational studies","volume":"196","author":"M Bayani","year":"2019","journal-title":"Acta Trop"},{"issue":"3","key":"pntd.0011350.ref009","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/acps.12423","article-title":"Beyond the association. 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