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.
