Spatial and temporal changes in the PGE2 EP2 receptor in mice hippocampi during postnatal development and its relationship with cyclooxygenase-2

Abstract

Objective(s): Prostaglandin E2 E-prostanoid 2 receptor (PGE2 EP2), downstream of cyclooxygenase-2 (COX-2), plays an important role in inflammatory responses, but there are some reports about synaptic functions of COX-2 and PGE2 EP2 in the hippocampus. Materials and Methods: C57BL/6J mice were sacrificed at postnatal days (P) 1, 7, 14, 28, and 56 for immunohistochemical staining for EP2 and doublecortin as well as western blot for EP2. In addition, COX-2 knockout and its wild-type mice were euthanized for immunohistochemical staining for EP2. Results: EP2 immunoreactivity was observed in the majority of the cells in the dentate gyrus at P1 and P7, while at P14, it was detected in the outer granule cell layer and was confined to its subgranular zone at P28 and P56. EP2 protein levels in the hippocampal homogenates were also highest at P7 and lowest at P56. EP2 immunoreactivity was partially colocalized, with doublecortin (DCX)-immunoreactive neuroblasts appearing in the mid-zone of the granule cell layer at P14 and in the subgranular zone of the dentate gyrus at P28. Co-localization of EP2 and DCX was significantly decreased in the dentate gyrus in the P28 group compared with that in the P14 group. In COX-2 knockout mice, EP2 immunoreactivity was significantly decreased in the hippocampal CA1 region (P=0.000165) and dentate gyrus (P=0.00898). Conclusion: EP2 decreases with age, which is expressed in DCX-immunoreactive neuroblasts in the dentate gyrus. This suggests that EP2 is closely linked to structural lamination and adult neurogenesis in the dentate gyrus.