Heterogeneity and convergence: the synaptic pathophysiology of autism.
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.
Biozentrum of the University of Basel, Basel, Switzerland; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK.
Stéphane J
SJ
Baudouin
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002659:Child Development Disorders, Pervasive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D018094:Receptors, Metabotropic Glutamate; C093438:neuroligin 1
Neuroligin; Prosap/Shank; autism spectrum disorders; genetic mouse models; metabotropic glutamate receptor type I; pathophysiology