brain    Neurobiology of Autism


A Fundamental Change in Autism is Synaptic Connectivity

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders. Mouse models of ASD gene mutations discovered in humans have consistently revealed aberrant synaptic function, typically expressed as a disruption in plasticity and alterations in the number and balance of excitatory and inhibitory connections. Therefore, irregularities in an “autistic” neuron may manifest as an increased or decreased number of synapses, which are either too strong or too weak. Interestingly, most of the ASD-related genetic mutations seem to not directly affect synapse structure, indicating that another level of control is dysregulated in ASD. Recently, emerging findings show alterations in protein expression in ASD, implicating a dysregulation in protein synthesis in the pathology of ASD.

Accumulating evidence has shown that alterations in neurite outgrowth and branching are a common phenotype in neurodevelopmental disorders including intellectual disability and ASD. Many autism-related mutations, such as those in phosphatase and tensin homolog on chromosome 10, tuberous sclerosis complex 1, or SHANK3, result in an excess of branching. Others, such as mutations in methyl CpG binding protein 2, thousand and one kinase 2, and endosomal Na+/H+  exchanger 6, lead to diminished branching.