Spatial and temporal changes in the PGE۲ EP۲ receptor in mice hippocampi during postnatal development and its relationship with cyclooxygenase-۲

Objective(s): Prostaglandin E۲ E-prostanoid ۲ receptor (PGE۲ EP۲), downstream of cyclooxygenase-۲ (COX-۲), plays an important role in inflammatory responses, but there are some reports about synaptic functions of COX-۲ and PGE۲ EP۲ in the hippocampus.Materials and Methods: C۵۷BL/۶J mice were sacrificed at postnatal days (P) ۱, ۷, ۱۴, ۲۸, and ۵۶ for immunohistochemical staining for EP۲ and doublecortin as well as western blot for EP۲. In addition, COX-۲ knockout and its wild-type mice were euthanized for immunohistochemical staining for EP۲.Results: EP۲ immunoreactivity was observed in the majority of the cells in the dentate gyrus at P۱ and P۷, while at P۱۴, it was detected in the outer granule cell layer and was confined to its subgranular zone at P۲۸ and P۵۶. EP۲ protein levels in the hippocampal homogenates were also highest at P۷ and lowest at P۵۶. EP۲ immunoreactivity was partially colocalized, with doublecortin (DCX)-immunoreactive neuroblasts appearing in the mid-zone of the granule cell layer at P۱۴ and in the subgranular zone of the dentate gyrus at P۲۸. Co-localization of EP۲ and DCX was significantly decreased in the dentate gyrus in the P۲۸ group compared with that in the P۱۴ group. In COX-۲ knockout mice, EP۲ immunoreactivity was significantly decreased in the hippocampal CA۱ region (P=۰.۰۰۰۱۶۵) and dentate gyrus (P=۰.۰۰۸۹۸). Conclusion: EP۲ decreases with age, which is expressed in DCX-immunoreactive neuroblasts in the dentate gyrus. This suggests that EP۲ is closely linked to structural lamination and adult neurogenesis in the dentate gyrus.

کلیدواژه ها:

Dentate gyrus ، Growth and Development ، Hippocampus ، Mice ، Prostaglandin E EP۲ subtype