Abstract
Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests, and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn) genes in humans has been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Syns are pre-synaptic proteins regulating synaptic vesicle traffic, neurotransmitter release, and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication, and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy.
Highlights
Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests, and repetitive behaviors
ASD IS ASSOCIATED WITH DYSFUNCTIONS IN CORTICAL CIRCUITS THAT PREDISPOSE TO EPILEPSY Autism spectrum disorder-like phenotypes are observed in a wide variety of neurological and neurodevelopmental disorders, including epilepsy, Rett syndrome, Fragile X Syndrome, Tuberous Sclerosis, or Fetal Anticonvulsant Syndrome, which are characterized by an imbalance of the excitatory/inhibitory tone
Similar to what occurs in children with ASDs and epilepsy, ASD-related behaviors in Syn I KO and Syn II KO mice precede the onset of seizures and epilepsy does not significantly affect the expression of the behavioral alterations in adult mice
Summary
ASD IS ASSOCIATED WITH DYSFUNCTIONS IN CORTICAL CIRCUITS THAT PREDISPOSE TO EPILEPSY Autism spectrum disorder-like phenotypes are observed in a wide variety of neurological and neurodevelopmental disorders, including epilepsy, Rett syndrome, Fragile X Syndrome, Tuberous Sclerosis, or Fetal Anticonvulsant Syndrome, which are characterized by an imbalance of the excitatory/inhibitory tone. This aspect is consistent with the very high prevalence of epilepsy in autistic patients (about 25%) with respect to the average prevalence of 1% in the general population. Given the importance of the excitation/inhibition balance in the activity-dependent formation and plasticity of neocortical networks, we here review on the role of the Syns, a family of presynaptic proteins regulating release and plasticity in inhibitory and excitatory synapses, in the etiology of ASDs and the use of Syn KO animals as a model for these complex neuropsychiatric disorders
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