Glutamate and neurotrophic factors in neuronal plasticity and disease

Mark P. Mattson

Research output: Chapter in Book/Report/Conference proceedingConference contribution

407 Scopus citations


Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell-surface glutamate receptors are coupled to Ca2+ influx and release from endoplasmic reticulum stores, which causes rapid (kinase- and protease-mediated) and delayed (transcription- dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca2+ homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca2+-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins, and antiapoptotic Bcl-2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Number of pages16
StatePublished - Nov 2008
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)00778923
ISSN (Electronic)17496632


  • Alzheimer's disease
  • AMPA receptors
  • BDNF
  • Calcium homeostasis
  • GDNF
  • Huntington's disease
  • NMDA
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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