The Dynamics of Hypothalamic Cell Proliferation in Mice

Abstract

Adult neurogenesis is the process by which new neurons are generated by neural stem cells (NSC) and are integrated into existing neural circuits in the adult brain. Contemporary research in adult neurogenesis in mammals has primarily focused on the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus, as these regions have the most robust cell proliferation. However, there also is evidence for neurogenic activity in other areas, including in the hypothalamus, which is a master regulator, maintaining homeostasis in many physiological and behavioral functions. The present studies tested whether the circadian clock influences the rate of cell proliferation in the hypothalamus, and compared the overall rate of proliferation in the median eminence (ME) (a subregion of the hypothalamus) with the rest of the hypothalamus. Mice were injected with the S-phase marker 5-bromo-2'- deoxyuridine (BrdU). A quantitative analysis of the resulting BrdU-labeled cells in the hypothalamus revealed a pronounced diurnal pattern of cell proliferation; the ME maintains a rhythm of proliferation that is distinct from the rest of the hypothalamus. In a 72-hour longitudinal study after a single BrdU pulse, stable numbers of BrdU+ cells were observed in the ME, with a corresponding increase in BrdU+ cells in the rest of the hypothalamus. These data suggest that circadian signals regulate the timing of hypothalamic cell proliferation, and that newly generated cells in the ME either migrate away or die, maintaining the stable numbers of BrdU+ cells in this region.