ROLE OF RELAXIN-3 IN ADULT HIPPOCAMPAL NEUROGENESIS

Abstract

Relaxin-3, a member of the insulin/relaxin superfamily, is predominantly expressed in a hindbrain region known as nucleus incertus, and is transmitted widely to numerous forebrain regions, including the hippocampus where adult neurogenesis occurs. Therefore, relaxin-3 is hypothesized to modulate adult hippocampal neurogenesis. To establish the role of relaxin-3 in neurogenesis, a loss-of-function approach was undertaken with relaxin-3 knockout (KO) mice, and to examine levels of neurogenesis, 5-bromo-2-deoxyuridine (BrdU) was administered to birth-date newborn cells. Quantitative analyses of BrdU revealed perturbed neurogenesis in the lifelong absence of relaxin-3, in an age-, sex- and septotemporal-dependent manner. In particular, in the temporal dentate gyrus, cell proliferation was downregulated in young adult male mice and mature adult female mice, while neuronal differentiation and migration were upregulated in mature adult male and female mice, respectively. These findings have demonstrated, for the first time, the necessity of relaxin-3 in the modulation of adult hippocampal neurogenesis.