Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome

Walter E. Kaufmann, Paul F. Worley, Christopher V. Taylor, Margaret Bremer, Peter C. Isakson

Research output: Contribution to journalArticle

Abstract

Cyclooxygenase or prostaglandin endoperoxide H synthase-2 (PGHS-2) is the first enzyme in the prostanoid biosynthetic pathways and, in brain, it is regulated as an immediate-early gene (IEG). PGHS-2 mRNA and protein are rapidly induced by physiological synaptic activity, and high basal expression in cerebral cortex appears to be maintained by the natural synaptic activity. In contrast to other IEGs, PGHS-2 is a dendritic protein that is enriched in dendritic spines and is, therefore, likely to play a direct role in synaptic physiology. Consistent with a signaling function in mature dendritic spines, PGHS-2 expression is strongly regulated during normal postnatal development in the rat, with peak expression during the third and fourth weeks. Here we use immunocytochemical approaches to compare the developmental expression of PGHS-2 in rat neocortex with that of other well characterized markers of dendritic maturation. PGHS-2 immunoreactivity (ir) follows histogenetic gradients and expression in secondary or more distal dendrites postdates that of even the most delayed dendritic proteins. This developmental pattern parallels the critical period for somatosensory and visual cortex development. Accordingly, PGHS-2-ir may be a useful marker of the final activity-dependent stages of cortical development. Consistent with this potential histochemical utility, we demonstrate that the normal laminar pattern of PGHS-2-ir in human cortex is altered in patients with Rett syndrome, a form of mental retardation with known alterations of dendritic maturation. Further studies of the developmental expression of PGHS-2 in human cortical development may permit analyses of dendritic abnormalities, in syndromes associated with disturbances of activity-dependent development, as well as provide an anatomic basis for understanding the role of prostaglandin signaling in cortical development.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalBrain and Development
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1997

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Keywords

  • Cyclooxygenase 2
  • Dendrite
  • Immediate-early gene
  • Monoclonal antibody
  • Neocortex
  • Postnatal development
  • Prostaglandin endoperoxide H synthase-2
  • Rett syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

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