CYCLOOXYGENASE-2 EXPRESSION DURING RAT NEOCORTICAL DEVELOPMENT AND INRETT-SYNDROME

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 pr otein are rapidly induced by physiological synaptic activity, and high basal expression in cerebral cortex appears to be maintained by the n atural synaptic activity. In contrast to other IEGs, PGHS-2 is a dendr itic protein that is enriched in dendritic spines and is, therefore, l ikely to play a direct role in synaptic physiology, Consistent with a signaling function in mature dendritic spines, PGHS-2 expression is st rongly regulated during normal postnatal development in the rat, with peak expression during the third and fourth weeks. Here we use immunoc ytochemical approaches to compare the developmental expression of PGHS -2 in rat neocortex with that of other well characterized markers of d endritic maturation. PGHS-2 immunoreactivity (ir) follows histogenetic gradients and expression in secondary or more distal dendrites postda tes that of even the most delayed dendritic proteins. This development al pattern parallels the critical period for somatosensory and visual cortex development, Accordingly, PGHS-2-ir may be a useful marker of t he final activity-dependent stages of cortical development. Consistent with this potential histochemical utility, we demonstrate that the no rmal laminar pattern of PGHS-2-ir in human cortex is altered in patien ts with Rett syndrome, a form of mental retardation with known alterat ions of dendritic maturation, Further studies of the developmental exp ression 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 deve lopment. (C) 1997 Elsevier Science B.V.