tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism
Autism 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 nerv...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13889 |
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| author | Hale Gök Dağıdır Neslihan Bukan Meltem Bahcelioglu Ayşen Çalıkuşu Ece Alim Saadet Özen Dizakar Elif Topa Hayrunnisa Bolay |
| author_facet | Hale Gök Dağıdır Neslihan Bukan Meltem Bahcelioglu Ayşen Çalıkuşu Ece Alim Saadet Özen Dizakar Elif Topa Hayrunnisa Bolay |
| author_sort | Hale Gök Dağıdır |
| collection | DOAJ |
| description | Autism 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 mg·kg−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‐1β and IL‐6 levels were significantly higher in male VPA‐exposed mice than controls. However, IL‐1β was significantly lower, and IL‐6, TNF‐ α, 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‐1β 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. |
| format | Article |
| id | doaj-art-851abfe8c0234c5d9369fddcb9e6e513 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-851abfe8c0234c5d9369fddcb9e6e5132025-01-07T02:27:34ZengWileyFEBS Open Bio2211-54632025-01-01151698010.1002/2211-5463.13889tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphismHale Gök Dağıdır0Neslihan Bukan1Meltem Bahcelioglu2Ayşen Çalıkuşu3Ece Alim4Saadet Özen Dizakar5Elif Topa6Hayrunnisa Bolay7Department of Medical Biochemistry, Faculty of Medicine Gazi University Ankara TurkeyDepartment of Medical Biochemistry, Faculty of Medicine Gazi University Ankara TurkeyFaculty of Medicine, Department of Anatomy, and Neuroscience and Neurotechnology Center of Excellence NÖROM Gazi University Ankara TurkeyDepartment of Neuroscience, Institute of Health Sciences Gazi University Ankara TurkeyFaculty of Medicine, Department of Anatomy, and Neuroscience and Neurotechnology Center of Excellence NÖROM Gazi University Ankara TurkeyDepartment of Histology and Embryology, Faculty of Medicine İzmir Bakırcay University TurkeyNeuropsychiatry Education, Research and Application Center (NPM) Gazi University Ankara TurkeyDepartment of Neurology and Algology, Neuropsychiatry Education, Research and Application Center (NPM), Neuroscience and Neurotechnology Center of Excellence NÖROM Gazi University Ankara TurkeyAutism 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 mg·kg−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‐1β and IL‐6 levels were significantly higher in male VPA‐exposed mice than controls. However, IL‐1β was significantly lower, and IL‐6, TNF‐ α, 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‐1β 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.https://doi.org/10.1002/2211-5463.13889autismbrain NLRP3cytokinesinflammationtransauricular vagal nerve stimulationVPA |
| spellingShingle | Hale Gök Dağıdır Neslihan Bukan Meltem Bahcelioglu Ayşen Çalıkuşu Ece Alim Saadet Özen Dizakar Elif Topa Hayrunnisa Bolay tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism FEBS Open Bio autism brain NLRP3 cytokines inflammation transauricular vagal nerve stimulation VPA |
| title | tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism |
| title_full | tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism |
| title_fullStr | tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism |
| title_full_unstemmed | tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism |
| title_short | tVNS alters inflammatory response in adult VPA‐induced mouse model of autism: evidence for sexual dimorphism |
| title_sort | tvns alters inflammatory response in adult vpa induced mouse model of autism evidence for sexual dimorphism |
| topic | autism brain NLRP3 cytokines inflammation transauricular vagal nerve stimulation VPA |
| url | https://doi.org/10.1002/2211-5463.13889 |
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