Dendritic Spine Pathology in Neuropsychiatric Disorders

Nat Neurosci. 2011 Mar;14(3):285-93. doi: 10.1038/nn.2741.

Abstract

Substantial progress has been made toward understanding the genetic architecture, cellular substrates, brain circuits and endophenotypic profiles of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia and Alzheimer's disease. Recent evidence implicates spiny synapses as important substrates of pathogenesis in these disorders. Although synaptic perturbations are not the only alterations relevant for these diseases, understanding the molecular underpinnings of spine pathology may provide insight into their etiologies and may reveal new drug targets. Here we discuss recent neuropathological, genetic, molecular and animal model studies that implicate structural alterations at spiny synapses in the pathogenesis of major neurological disorders, focusing on ASD, schizophrenia and Alzheimer's disease as representatives of these categories across different ages of onset. We stress the importance of reverse translation, collaborative and multidisciplinary approaches, and the study of the spatio-temporal roles of disease molecules in the context of synaptic regulatory pathways and neuronal circuits that underlie disease endophenotypes.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Animals
  • Dendritic Spines / pathology*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nervous System Diseases / genetics
  • Nervous System Diseases / pathology*
  • Nervous System Diseases / physiopathology
  • Schizophrenia / genetics
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology

Substances

  • Nerve Tissue Proteins