Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan

T. B. Romanczyk, Cynthia Shannon Weickert, M. J. Webster, M. M. Herman, M. Akil, J. E. Kleinman

Research output: Contribution to journalArticle

Abstract

Signalling through tyrosine kinase receptor B (trkB) influences neuronal survival, differentiation and synaptogenesis. trkB exists in a full-length form (trkBTK+), which contains a catalytic tyrosine kinase (TK) domain, and a truncated form (trkBTK-), which lacks this domain. In the rodent brain, expression of trkBTK+ decreases and trkBTK- increases during postnatal life. We hypothesized that both forms of trkB receptor mRNA would be present in the human neocortex and that the developmental profile of trkB gene expression in human may be distinct from that in rodent. We detected both trkBTK+ and trkBTK- mRNA in RNA extracted from multiple human brain regions by Northern blot. Using in situ hybridization, we found trkBTK+ mRNA in all cortical layers, with highest expression in layer IV and intermediate-to-high expression in layers III and V of the human dorsolateral prefrontal cortex. trkBTK+ mRNA was present in neurons with both pyramidal and nonpyramidal shapes in the dorsolateral prefrontal cortex. trkBTK+ mRNA levels were significantly increased in layer III in young adults as compared with infants and the elderly. In the elderly, trkBTK+ mRNA levels were reduced markedly in all cortical layers. Unlike the mRNA encoding the full-length form of trkB, trkBTK- mRNA was distributed homogeneously across the grey matter, and trkBTK- mRNA levels increased only slightly during postnatal life. The results suggest that neurons in the human dorsolateral prefrontal cortex are responsive to neurotrophins throughout postnatal life and that this responsiveness may be modulated during the human lifespan.

Original languageEnglish (US)
Pages (from-to)269-280
Number of pages12
JournalEuropean Journal of Neuroscience
Volume15
Issue number2
DOIs
StatePublished - Dec 31 2002
Externally publishedYes

Keywords

  • Ageing
  • BDNF receptor
  • Development
  • Gene expression
  • Growth factor
  • Neurotrophin
  • Postmortem
  • Puberty
  • Senescence
  • Truncated trkB

ASJC Scopus subject areas

  • Neuroscience(all)

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