Antisense Noggin oligodeoxynucleotide administration decreases cell proliferation in the dentate gyrus of adult rats.

The dentate gyrus of the hippocampus is one of few regions in the adult mammalian brain characterized by ongoing neurogenesis. It has been demonstrated that Noggin antagonizes bone morphogenetic protein-4 (BMP4) to create a niche for subventricular zone neurogenesis. We previously demonstrated that Noggin and BMP4 showed strong expression in the proliferative subgranular layer of the dentate gyrus in adult rats. To examine the action of Noggin on cell proliferation in the dentate gyrus of adult rats, we administered antisense oligodeoxynucleotide (ASODN) to Noggin by continuous infusion into the lateral ventricle of rats. Antisense-infused rats displayed significant reduction in number of bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus. This indicated that endogenous Noggin activity is important for naturally occurring cell proliferation in the dentate gyrus, and perhaps neurogenesis, and is one of the many factors involved in its regulation.