The glutamate synapse in neuropsychiatric disorders. Focus on schizophrenia and Alzheimer's disease

Prog Brain Res. 1998:116:421-37. doi: 10.1016/s0079-6123(08)60453-7.

Abstract

Here we have described a novel excitotoxic process in which hypofunctional NMDA receptors cease driving GABA ergic neurons which cease inhibiting excitatory transmitters in the brain. These disinhibited excitatory transmitters then act in concert to slowly hyperstimulate neurons in corticolimbic brain regions. We have discussed how such an abnormality could exist in the brains of individuals with schizophrenia or AD and could account for the clinical stigmata of the two disorders. In addition, we have highlighted how other disorder-specific factors would account for the differences in the clinical presentation of AD and schizophrenia. In an animal model, pharmacological methods have been developed for preventing the overstimulation of these vulnerable corticolimbic pyramidal neurons and at least some of these methods may be applicable for treating AD and schizophrenia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / physiopathology*
  • Animals
  • Glutamic Acid / physiology*
  • Humans
  • Mental Disorders / physiopathology*
  • Schizophrenia / physiopathology*
  • Synapses / physiology*

Substances

  • Glutamic Acid