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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1447385
This article is part of the Research Topic Bone Marrow Aging and its Impact on Immunosenescence in Neurological Diseases View all articles

Immune system dysfunction and inflammation in aging Shank3b mutant mice, a model of autism spectrum disorder

Provisionally accepted
Enrica Cerilli Enrica Cerilli 1Ginevra M. Dall'O' Ginevra M. Dall'O' 1Gabriele Chelini Gabriele Chelini 1,2Benedetta Catena Benedetta Catena 1Birgit Weinberger Birgit Weinberger 3Yuri Bozzi Yuri Bozzi 1*Luca Pangrazzi Luca Pangrazzi 1,3*
  • 1 Centre for Mind and Brain Sciences, University of Trento, Rovereto, Trentino-Alto Adige, Italy
  • 2 Institute of Neuroscience, National Research Council (CNR), Pisa, Tuscany, Italy
  • 3 Institute for Biomedical Aging Research, Faculty of Biology, University of Innsbruck, Innsbruck, Austria

The final, formatted version of the article will be published soon.

    Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental conditions characterized by deficits in social interaction/communication and restrictive/repetitive behaviors. Recent studies highlight the role of immune system dysfunction and inflammation in ASD pathophysiology. Indeed, elevated levels of proinflammatory cytokines were described in the brain and peripheral blood of ASD individuals. Despite this, how this pro-inflammatory profile evolves with aging and whether it may be associated with behavioral deficits is unknown. In this work, we explored the impact of aging on motor behavior and inflammation using Shank3b mutant mice, a model for syndromic ASD. Using RT-qPCR and flow cytometry, we examined the expression of key pro-inflammatory molecules in the cerebellum, bone marrow, spleen, and peripheral blood, comparing adult and old Shank3b +/+ , Shank3b +/-, and Shank3b -/-mice. Our findings revealed genotype-and age-related differences in inflammation and motor behavior, with Shank3b -/-mice exhibiting accelerated aging and motor impairments. Correlations between pro-inflammatory molecules and behavioral deficits suggest that a link may be present between systemic inflammation and ASD-related behaviors, underscoring the potential role of agerelated inflammation ("inflammaging") in exacerbating ASD symptoms.

    Keywords: neurodevelopmental disorder, Inflammaging, Bone Marrow, Spleen, Cerebellum, Brain

    Received: 11 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Cerilli, Dall'O', Chelini, Catena, Weinberger, Bozzi and Pangrazzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yuri Bozzi, Centre for Mind and Brain Sciences, University of Trento, Rovereto, 38068, Trentino-Alto Adige, Italy
    Luca Pangrazzi, Institute for Biomedical Aging Research, Faculty of Biology, University of Innsbruck, Innsbruck, Austria

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