Catechol-o-methyltransferase enzyme activity and protein expression in human prefrontal cortex across the postnatal lifespan

E. M. Tunbridge, C. S. Weickert, J. E. Kleinman, M. M. Herman, J. Chen, B. S. Kolachana, P. J. Harrison, D. R. Weinberger

Research output: Contribution to journalArticlepeer-review

Abstract

The prefrontal cortex (PFC) dopamine system, which is critical for modulating PFC function, undergoes remodeling until at least young adulthood in primates. Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val 158Met) that has been associated with variation in PFC function. We examined COMT enzyme activity and protein immunoreactivity in the PFC during human postnatal development. Protein was extracted from PFC of normal individuals from 6 age groups: neonates (1-4 months), infants (5-11 months), teens (14-18 years), young adults (20-24 years), adults (31-43 years), and aged individuals (68-86 years; n = 5-8 per group). There was a significant 2-fold increase in COMT enzyme activity from neonate to adulthood, paralleled by increases in COMT protein immunoreactivity. Furthermore, COMT protein immunoreactivity was related to Val158Met genotype, as has been previously demonstrated. The significant increase in COMT activity from neonate to adulthood complements previous findings of protracted postnatal changes in the PFC dopamine system and may reflect an increasing importance of COMT for PFC dopamine regulation during maturation.

Original languageEnglish (US)
Pages (from-to)1206-1212
Number of pages7
JournalCerebral Cortex
Volume17
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • COMT
  • Development
  • Dopamine
  • Schizophrenia

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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