Cell Biology of BDNF and its Relevance to Schizophrenia

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

BDNF is a key regulator of synaptic plasticity and hence is thought to be uniquely important for various cognitive functions. While correlations of schizophrenia with polymorphisms in the BDNF gene and changes in BDNF mRNA levels have been reported, specific links remain to be established. Cell biology studies may provide clues as to how BDNF signalling impacts schizophrenia aetiology and pathogenesis: (1) the Val-Met polymorphism in the pro-domain affects activity-dependent BDNF secretion and short-term, hippocampus-mediated episodic memory. (2) pro-BDNF and mBDNF, by interacting with their respective p75NTR and TrkB receptors, facilitate long-term depression (LTD) and long-term potentiation (LTP), two common forms of synaptic plasticity working in opposing directions. (3) BDNF transcription is controlled by four promoters, which drive expression of four BDNF-encoding transcripts in different brain regions, cell types and subcellular compartments (dendrites, cell body, etc.), and each is regulated by different genetic and environmental factors. A role for BDNF in early- and late-phase LTP and short- and long-term, hippocampal-dependent memory has been firmly established. Extending these studies to synaptic plasticity in other areas of the brain may help us to better understand how altered BDNF signalling could contribute to intermediate phenotypes associated with schizophrenia.

Original languageEnglish (US)
Title of host publicationGrowth Factors and Psychiatric Disorders
Publisherwiley
Pages119-129
Number of pages11
Volume289
ISBN (Electronic)9780470751251
ISBN (Print)9780470516041
DOIs
StatePublished - May 20 2008
Externally publishedYes

Keywords

  • BDNF splice variants
  • Brain derived neurotrophic factor
  • Dendrites
  • Epilepsy
  • Extrasomatic protein synthesis
  • Hippocampus
  • Mood disorders
  • MRNA transport
  • Neurotrophins
  • Visual cortex

ASJC Scopus subject areas

  • Medicine(all)

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