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GA I patients present progressive neurological deterioration whose pathophysiology is only partially elucidated. We investigated whether intracerebral GA administration, alone or combined with quinolinic acid (QA), a pro-inflammatory intermediate of the kynurenine pathway, could alter the expression of genes associated with inflammatory signaling, endoplasmic reticulum (ER) stress, and neurotrophic support in cerebral cortex of wild-type (WT) and\n                    <jats:italic>Gcdh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. We also tested the effects of L-carnitine (Carn) on these parameters. GA alone increased mRNA levels of the genes encoding NF-\u03baB (\n                    <jats:italic>NFKB1<\/jats:italic>\n                    ), COX-2 (\n                    <jats:italic>PTGS2<\/jats:italic>\n                    ), iNOS (\n                    <jats:italic>NOS2<\/jats:italic>\n                    ), and TLR2 (\n                    <jats:italic>TLR2<\/jats:italic>\n                    ) in both genotypes, while reducing those of IL-10 (\n                    <jats:italic>IL10<\/jats:italic>\n                    ) and VEGF-A (\n                    <jats:italic>VEGFA<\/jats:italic>\n                    ) only in Gcdh\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Combined QA\u2009+\u2009GA treatment produced a larger response, including increased TNF-\u03b1 (\n                    <jats:italic>TNF<\/jats:italic>\n                    ), IL-1\u03b2 (\n                    <jats:italic>IL1B<\/jats:italic>\n                    ), IL-6 (\n                    <jats:italic>IL6<\/jats:italic>\n                    )\n                    <jats:italic>,<\/jats:italic>\n                    NLRP3 (\n                    <jats:italic>NLRP3<\/jats:italic>\n                    ), CHOP (\n                    <jats:italic>DDIT3<\/jats:italic>\n                    ) and PERK (\n                    <jats:italic>EIF2AK3<\/jats:italic>\n                    ) mRNA levels in the Gcdh\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, besides reducing I\u03baB\u03b1 (\n                    <jats:italic>NFKBIA<\/jats:italic>\n                    ), IL-10 (\n                    <jats:italic>IL10<\/jats:italic>\n                    ) and BDNF (\n                    <jats:italic>BDNF<\/jats:italic>\n                    ) expression in both genotypes, and VEGF-A (\n                    <jats:italic>VEGFA<\/jats:italic>\n                    ) in the\n                    <jats:italic>Gcdh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. We also found that lysine (Lys) and QA treatment elevated TNF-\u03b1, IL-1\u03b2, and IL-6 protein levels in\n                    <jats:italic>Gcdh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Carn prevented or attenuated most transcriptional alterations induced by QA\u2009+\u2009GA and reduced cytokine protein elevations elicited by Lys\u2009+\u2009QA administration. These findings indicate that Carn modulates acute molecular responses related to inflammation, ER stress, and neurotrophic factors in the cerebral cortex of the GAI mouse model.\n                  <\/jats:p>","DOI":"10.1007\/s11011-026-01973-y","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:52:29Z","timestamp":1788587549000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["L-carnitine modulates molecular responses associated with inflammation, endoplasmic reticulum stress, and neurotrophic signaling in cerebral cortex of neonatal Gcdh\u2212\/\u2212 mice exposed to glutaric and quinolinic acids"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2358-6695","authenticated-orcid":false,"given":"Ediandra Tissot","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5648-4997","authenticated-orcid":false,"given":"\u00c2ngela","family":"Zanatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-668X","authenticated-orcid":false,"given":"Andrey Vinicios Soares","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9849-9454","authenticated-orcid":false,"given":"Amanda Uggeri","family":"de Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0596-5667","authenticated-orcid":false,"given":"Carlos Alexandre","family":"Netto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-8923","authenticated-orcid":false,"given":"Guilhian","family":"Leipnitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-0714","authenticated-orcid":false,"given":"Alexandre Umpierrez","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-0654","authenticated-orcid":false,"given":"Carmen Regla","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-6369","authenticated-orcid":false,"given":"Rafael Teixeira","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-1807","authenticated-orcid":false,"given":"Moacir","family":"Wajner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"1973_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.ymgme.2012.04.015","volume":"107","author":"AU Amaral","year":"2012","unstructured":"Amaral AU, Cecatto C, Seminotti B et al (2012a) Marked reduction of Na+, K+-ATPase and creatine kinase activities induced by acute lysine administration in glutaryl-CoA dehydrogenase deficient mice. 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