tVNS alters inflammatory response in adult VPA-induced mouse model of autism: evidence for sexual dimorphism

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dc.authoridBolay, Hayrunnisa/0000-0002-3357-7733
dc.authoridALIM, ECE/0000-0002-4686-0677
dc.authoridBAHCELIOGLU, Meltem/0000-0001-5279-3450
dc.authoridCALIKUSU, Aysen/0000-0003-0313-1906
dc.contributor.authorDagidir, Hale Gok
dc.contributor.authorBukan, Neslihan
dc.contributor.authorBahcelioglu, Meltem
dc.contributor.authorCalikusu, Aysen
dc.contributor.authorAlim, Ece
dc.contributor.authorDizakar, Saadet Ozen
dc.contributor.authorTopa, Elif
dc.date.accessioned2025-03-20T09:51:26Z
dc.date.available2025-03-20T09:51:26Z
dc.date.issued2025
dc.departmentİzmir Bakırçay Üniversitesi
dc.description.abstractAutism is a neurodevelopmental disorder with limited treatment alternatives and which incidence is increasing. Some research suggests that vagus nerve simulation might lead to the reduction of certain symptom. Therefore, we aimed to examine the effect of bilateral transcutaneous auricular vagus nerve stimulation (tVNS) on the inflammatory response in an adult valproic acid (VPA) induced mouse (C57BL6) model of autism for the first time. The autism model was induced by oral VPA administration (600 mgkg(-1)) to C57BL/6 pregnant mice on E12.5 days. The study included three groups: the VPA Transcutaneous Auricular Stimulation Group (VPA + tVNS), the VPA Control Group (VPA + sham), and the Healthy Control Group (Control + sham). Each group included 16 mice (8 M/8 F). Our results show that serum IL-1 beta and IL-6 levels were significantly higher in male VPA-exposed mice than controls. However, IL-1 beta was significantly lower, and IL-6, TNF- alpha, and IL-22 were not different in female VPA-exposed mice compared to the control group. Brain NLRP3 levels were significantly higher in both sexes in the VPA autism model (P < 0.05). tVNS application increased brain NLRP3 levels in both sexes and reduced serum IL-1 beta levels in male mice. We conclude that cytokine dysregulation is associated with the VPA-induced adult autism model, and the inflammatory response is more pronounced in male mice. tVNS application altered the inflammatory response and increased brain NLPR3 levels in both sexes. Further studies are needed to understand the beneficial or detrimental role of the inflammatory response in autism and its sexual dimorphism.
dc.description.sponsorshipGazi University Scientific Research Projects Coordination Unit (BAP) [TDK-2021-7245, 76/2020-01]; TUBA (Turkish Academy of Science); TUBA; YOK 100-2000 Human Brain and Neuroscience program scholarship
dc.description.sponsorshipThis study was supported by Gazi University Scientific Research Projects Coordination Unit (BAP) (Project Numbers: TDK-2021-7245 and 76/2020-01) and partially supported by TUBA (Turkish Academy of Science). The Article Processing Charge (APC) was supported by the TUBA. Researchers Hale Goek Da & gbreve;& imath;d & imath;r and Ay & scedil;en Cal & imath;ku & scedil;u were supported by the YOK 100-2000 Human Brain and Neuroscience program scholarship. We would like to express our gratitude to Dr & Idot;lkem Guezel for his valuable support in graphic design.
dc.identifier.doi10.1002/2211-5463.13889
dc.identifier.endpage80
dc.identifier.issn2211-5463
dc.identifier.issue1
dc.identifier.pmid39401991
dc.identifier.scopus2-s2.0-85206262742
dc.identifier.scopusqualityQ2
dc.identifier.startpage69
dc.identifier.urihttps://doi.org/10.1002/2211-5463.13889
dc.identifier.urihttps://hdl.handle.net/20.500.14034/2544
dc.identifier.volume15
dc.identifier.wosWOS:001338613100001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofFebs Open Bio
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250319
dc.subjectautism
dc.subjectbrain NLRP3
dc.subjectcytokines
dc.subjectinflammation
dc.subjecttransauricular vagal nerve stimulation
dc.subjectVPA
dc.titletVNS alters inflammatory response in adult VPA-induced mouse model of autism: evidence for sexual dimorphism
dc.typeArticle

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