N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder
Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stres...
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MDPI AG
2024-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/11/1390 |
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| author | Luca Pangrazzi Enrica Cerilli Luigi Balasco Ginevra Matilde Dall’O’ Gabriele Chelini Anna Pastore Birgit Weinberger Yuri Bozzi |
| author_facet | Luca Pangrazzi Enrica Cerilli Luigi Balasco Ginevra Matilde Dall’O’ Gabriele Chelini Anna Pastore Birgit Weinberger Yuri Bozzi |
| author_sort | Luca Pangrazzi |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated <i>Shank3b<sup>−/−</sup></i> animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder. |
| format | Article |
| id | doaj-art-f01dbb75527c4ffb9f22e47dd3c3b5b2 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-f01dbb75527c4ffb9f22e47dd3c3b5b22024-11-26T17:47:15ZengMDPI AGAntioxidants2076-39212024-11-011311139010.3390/antiox13111390N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum DisorderLuca Pangrazzi0Enrica Cerilli1Luigi Balasco2Ginevra Matilde Dall’O’3Gabriele Chelini4Anna Pastore5Birgit Weinberger6Yuri Bozzi7Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020 Innsbruck, AustriaCIMeC—Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, ItalyCIMeC—Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, ItalyCIMeC—Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, ItalyCIMeC—Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, ItalyMetabolomics and Proteomics Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, 00168 Rome, ItalyInstitute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020 Innsbruck, AustriaCIMeC—Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, ItalyAutism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated <i>Shank3b<sup>−/−</sup></i> animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.https://www.mdpi.com/2076-3921/13/11/1390autisminflammationROScerebellumNAC |
| spellingShingle | Luca Pangrazzi Enrica Cerilli Luigi Balasco Ginevra Matilde Dall’O’ Gabriele Chelini Anna Pastore Birgit Weinberger Yuri Bozzi N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder Antioxidants autism inflammation ROS cerebellum NAC |
| title | N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder |
| title_full | N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder |
| title_fullStr | N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder |
| title_full_unstemmed | N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder |
| title_short | N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder |
| title_sort | n acetylcysteine counteracts immune dysfunction and autism related behaviors in the shank3b mouse model of autism spectrum disorder |
| topic | autism inflammation ROS cerebellum NAC |
| url | https://www.mdpi.com/2076-3921/13/11/1390 |
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