Abstract
Intellectual disability (ID) and autism are present in several neurodevelopmental disorders and are often associated in genetic syndromes, such as Fragile X and Rett syndromes. While most evidence indicates that a genetic component plays an important role in the aetiology of both autism and ID, a number of studies suggest that immunological dysfunctions may participate in the pathophysiology of these disorders. Brain-specific autoantibodies have been detected in the sera of many autistic children and autoimmune disorders are increased in families of children with autism. Furthermore, cytokine imbalance has been reported in children with autism. These results may reflect an inappropriate immune response to environmental factors, such as infectious or toxic exposure. The role of microglia as sensors of pre- and post-natal environmental stimuli and its involvement in the regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis has recently emerged. An abnormal immune response during critical windows of development and consequent abnormal production of neuro-inflammatory mediators may have an impact on the function and structure of brain and can play a role in the pathogenesis of non syndromic autism. Recent evidence suggests an involvement of neuro-inflammation also in syndromic forms of autism and ID. Immune dysregulation has been found in children with Fragile X syndrome and an intrinsic microglia dysfunction has been recently reported in Rett syndrome. The present review summarizes the current literature suggesting that neuro-inflammatory mechanisms may contribute to the pathogenesis of different ID- and autism-associated disorders, thus representing common pathophysiological pathways and potential therapeutic targets.
Keywords: Neurodevelopment, cytokines, immune cells, microglia, astrocytes, gliosis, autism, mental retardation.
CNS & Neurological Disorders - Drug Targets
Title:Neuro-Inflammatory Mechanisms in Developmental Disorders Associated with Intellectual Disability and Autism Spectrum Disorder: A Neuro- Immune Perspective
Volume: 15 Issue: 4
Author(s): Barbara Di Marco, Carmela M. Bonaccorso, Elisabetta Aloisi, Simona D’Antoni and Maria V. Catania
Affiliation:
Keywords: Neurodevelopment, cytokines, immune cells, microglia, astrocytes, gliosis, autism, mental retardation.
Abstract: Intellectual disability (ID) and autism are present in several neurodevelopmental disorders and are often associated in genetic syndromes, such as Fragile X and Rett syndromes. While most evidence indicates that a genetic component plays an important role in the aetiology of both autism and ID, a number of studies suggest that immunological dysfunctions may participate in the pathophysiology of these disorders. Brain-specific autoantibodies have been detected in the sera of many autistic children and autoimmune disorders are increased in families of children with autism. Furthermore, cytokine imbalance has been reported in children with autism. These results may reflect an inappropriate immune response to environmental factors, such as infectious or toxic exposure. The role of microglia as sensors of pre- and post-natal environmental stimuli and its involvement in the regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis has recently emerged. An abnormal immune response during critical windows of development and consequent abnormal production of neuro-inflammatory mediators may have an impact on the function and structure of brain and can play a role in the pathogenesis of non syndromic autism. Recent evidence suggests an involvement of neuro-inflammation also in syndromic forms of autism and ID. Immune dysregulation has been found in children with Fragile X syndrome and an intrinsic microglia dysfunction has been recently reported in Rett syndrome. The present review summarizes the current literature suggesting that neuro-inflammatory mechanisms may contribute to the pathogenesis of different ID- and autism-associated disorders, thus representing common pathophysiological pathways and potential therapeutic targets.
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Marco Di Barbara, Bonaccorso M. Carmela, Aloisi Elisabetta, D’Antoni Simona and Catania V. Maria, Neuro-Inflammatory Mechanisms in Developmental Disorders Associated with Intellectual Disability and Autism Spectrum Disorder: A Neuro- Immune Perspective, CNS & Neurological Disorders - Drug Targets 2016; 15 (4) . https://dx.doi.org/10.2174/1871527315666160321105039
DOI https://dx.doi.org/10.2174/1871527315666160321105039 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |

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