title: Comparison of pharmacological and genetic inhibition of cyclooxygenase-2: effects on adult neurogenesis in the hippocampal dentate gyrus.
abstract: Inducible cyclooxygenase-2 (COX-2) has received much attention because of its role in neuro-inflammation and synaptic plasticity. Even though COX-2 levels are high in healthy animals, the function of this factor in adult neurogenesis has not been clearly demonstrated. Therefore, we performed the present study to compare the effects of pharmacological and genetic inhibition of COX-2 on adult hippocampal neurogenesis. Physiological saline or the same volume containing celecoxib was administered perorally every day for 5 weeks using a feeding needle. Compared to the control, pharmacological and genetic inhibition of COX-2 reduced the appearance of nestin-immunoreactive neural stem cells, Ki67-positive nuclei, and doublecortin-immunoreactive neuroblasts in the dentate gyrus. In addition, a decrease in phosphorylated cAMP response element binding protein (pCREB) at Ser133 was observed. Compared to pharmacological inhibition, genetic inhibition of COX-2 resulted in significant reduction of neural stem cells, cell proliferation, and neuroblast differentiation as well as pCREB levels. These results suggest that COX-2 is part of the molecular machinery that regulates neural stem cells, cell proliferation, and neuroblast differentiation during adult hippocampal neurogenesis via pCREB. Additionally, genetic inhibition of COX-2 strongly reduced neural stem cell populations, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to pharmacological inhibition.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Jong Whi
authors.initials: JW
authors.lastname: Kim
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000068579:Celecoxib / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: cell proliferation; cyclooxygenase-2; hippocampus; neural stem cells; neuroblast differentiation