Dendritic spine dysgenesis in autism related disorders

Neurosci Lett. 2015 Aug 5;601:30-40. doi: 10.1016/j.neulet.2015.01.011. Epub 2015 Jan 8.

Abstract

The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target.

Keywords: Fragile X; Intellectual disability; MeCP2; Rett syndrome; TrkB; mGluR; mTOR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angelman Syndrome / complications
  • Angelman Syndrome / pathology
  • Animals
  • Child Development Disorders, Pervasive / complications
  • Child Development Disorders, Pervasive / pathology*
  • Dendritic Spines / pathology*
  • Dendritic Spines / physiology
  • Down Syndrome / complications
  • Down Syndrome / pathology
  • Fragile X Syndrome / complications
  • Fragile X Syndrome / pathology
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / pathology*
  • Rett Syndrome / complications
  • Rett Syndrome / pathology
  • Tuberous Sclerosis / complications
  • Tuberous Sclerosis / pathology