Heterogeneity and convergence: the synaptic pathophysiology of autism

Eur J Neurosci. 2014 Apr;39(7):1107-13. doi: 10.1111/ejn.12498.

Abstract

Autism is a developmental disorder characterised by a high heterogeneity of clinical diagnoses and genetic associations. This heterogeneity is a challenge for the identification of the pathophysiology of the disease and for the development of new therapeutic strategies. New conceptual approaches are being used to try to challenge this complexity and gene cluster analysis studies suggest that the pathophysiology of autism is associated with a dysregulation of specific cellular mechanisms. This review will present the experimental evidence for a convergence of synaptic pathophysiology between syndromic and non-syndromic forms of autism, grouped under the generic term of autism spectrum disorders. In particular I will highlight the results from genetic mouse models identifying a convergence of dysregulation of the synaptic type I metabotropic glutamate receptor pathway in mouse models for autism spectrum disorders. These results help to build a new conceptual framework for the study of the synaptic phenotype of autism, which is important for the identification of new therapeutic strategies.

Keywords: Neuroligin; Prosap/Shank; autism spectrum disorders; genetic mouse models; metabotropic glutamate receptor type I; pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Child Development Disorders, Pervasive / genetics
  • Child Development Disorders, Pervasive / metabolism
  • Child Development Disorders, Pervasive / physiopathology*
  • Humans
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism
  • Synapses / metabolism*
  • Synapses / physiology

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Receptors, Metabotropic Glutamate
  • neuroligin 1