Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies

Int J Mol Sci. 2020 Dec 23;22(1):59. doi: 10.3390/ijms22010059.

Abstract

The correlation between dysfunction in the glutamatergic system and neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, is undisputed. Both disorders are associated with molecular and ultrastructural alterations that affect synaptic plasticity and thus the molecular and physiological basis of learning and memory. Altered synaptic plasticity, accompanied by changes in protein synthesis and trafficking of postsynaptic proteins, as well as structural modifications of excitatory synapses, are critically involved in the postnatal development of the mammalian nervous system. In this review, we summarize glutamatergic alterations and ultrastructural changes in synapses in schizophrenia and autism spectrum disorder of genetic or drug-related origin, and briefly comment on the possible reversibility of these neuropsychiatric disorders in the light of findings in regular synaptic physiology.

Keywords: autism spectrum disorder; glutamatergic system; schizophrenia; synaptic ultrastructure.

Publication types

  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / etiology*
  • Autism Spectrum Disorder / metabolism*
  • Biomarkers
  • Disease Models, Animal
  • Disease Susceptibility
  • Glutamic Acid / metabolism*
  • Humans
  • Mitochondria / metabolism
  • Neuronal Plasticity
  • Neurons / metabolism
  • Receptors, Glutamate / metabolism*
  • Rodentia
  • Schizophrenia / etiology*
  • Schizophrenia / metabolism*
  • Synapses / metabolism*
  • Synapses / pathology
  • Synapses / ultrastructure*

Substances

  • Biomarkers
  • Receptors, Glutamate
  • Glutamic Acid