Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders
Among the proposed mechanisms for autism spectrum disorders (ASD) is immune dysregulation. The proinflammatory cytokine Interleukine-17A (IL-17A) was shown to play a key role in mediating immune-related neurodevelopmental impairment of social behavior. Nevertheless, post-developmental administration...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/432 |
| _version_ | 1797358644165083136 |
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| author | Yehoshua Willinger Daniella R. Friedland Cohen Gadi Turgeman |
| author_facet | Yehoshua Willinger Daniella R. Friedland Cohen Gadi Turgeman |
| author_sort | Yehoshua Willinger |
| collection | DOAJ |
| description | Among the proposed mechanisms for autism spectrum disorders (ASD) is immune dysregulation. The proinflammatory cytokine Interleukine-17A (IL-17A) was shown to play a key role in mediating immune-related neurodevelopmental impairment of social behavior. Nevertheless, post-developmental administration of IL-17A was found to increase social behavior. In the present study, we explored the effect of post-developmental administration of IL-17A on ASD-like behaviors induced by developmental exposure to valproic acid (VPA) at postnatal day 4. At the age of seven weeks, VPA-exposed mice were intravenously injected twice with recombinant murine IL-17A (8 μg), and a week later, they were assessed for ASD-like behavior. IL-17A administration increased social behavior and alleviated the ASD-like phenotype. Behavioral changes were associated with increased serum levels of IL-17 and Th17-related cytokines. Exogenous IL-17A also increased neuritogenesis in the dendritic tree of doublecortin-expressing newly formed neurons in the dentate gyrus. Interestingly, the effect of IL-17A on neuritogenesis was more noticeable in females than in males, suggesting a sex-dependent effect of IL-17A. In conclusion, our study suggests a complex role for IL-17A in ASD. While contributing to its pathology at the developmental stage, IL-17 may also promote the alleviation of behavioral deficits post-developmentally by promoting neuritogenesis and synaptogenesis in the dentate gyrus. |
| first_indexed | 2024-03-08T15:05:01Z |
| format | Article |
| id | doaj.art-1aa82f2f0d084a52885c575a8f2f0834 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:01Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1aa82f2f0d084a52885c575a8f2f08342024-01-10T14:59:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125143210.3390/ijms25010432Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum DisordersYehoshua Willinger0Daniella R. Friedland Cohen1Gadi Turgeman2Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, IsraelDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, IsraelDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, IsraelAmong the proposed mechanisms for autism spectrum disorders (ASD) is immune dysregulation. The proinflammatory cytokine Interleukine-17A (IL-17A) was shown to play a key role in mediating immune-related neurodevelopmental impairment of social behavior. Nevertheless, post-developmental administration of IL-17A was found to increase social behavior. In the present study, we explored the effect of post-developmental administration of IL-17A on ASD-like behaviors induced by developmental exposure to valproic acid (VPA) at postnatal day 4. At the age of seven weeks, VPA-exposed mice were intravenously injected twice with recombinant murine IL-17A (8 μg), and a week later, they were assessed for ASD-like behavior. IL-17A administration increased social behavior and alleviated the ASD-like phenotype. Behavioral changes were associated with increased serum levels of IL-17 and Th17-related cytokines. Exogenous IL-17A also increased neuritogenesis in the dendritic tree of doublecortin-expressing newly formed neurons in the dentate gyrus. Interestingly, the effect of IL-17A on neuritogenesis was more noticeable in females than in males, suggesting a sex-dependent effect of IL-17A. In conclusion, our study suggests a complex role for IL-17A in ASD. While contributing to its pathology at the developmental stage, IL-17 may also promote the alleviation of behavioral deficits post-developmentally by promoting neuritogenesis and synaptogenesis in the dentate gyrus.https://www.mdpi.com/1422-0067/25/1/432autism spectrum disorder (ASD)hippocampal neurogenesisIL-17Asocial behavior |
| spellingShingle | Yehoshua Willinger Daniella R. Friedland Cohen Gadi Turgeman Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders International Journal of Molecular Sciences autism spectrum disorder (ASD) hippocampal neurogenesis IL-17A social behavior |
| title | Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders |
| title_full | Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders |
| title_fullStr | Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders |
| title_full_unstemmed | Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders |
| title_short | Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders |
| title_sort | exogenous il 17a alleviates social behavior deficits and increases neurogenesis in a murine model of autism spectrum disorders |
| topic | autism spectrum disorder (ASD) hippocampal neurogenesis IL-17A social behavior |
| url | https://www.mdpi.com/1422-0067/25/1/432 |
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