Martine Migaud

Hypothalamic neurogenesis and seasonal control of reproduction 

Adult neurogenesis is recognized as the process of producing new neurons from adult neural stem cells. The hypothalamus, a structure critically involved in the control of neuroendocrine functions, ranging from reproduction, to energy intake/expenditure balance, has recently been shown to harbor adult neural stem cells within a neurogenic niche. In the ependymal lining of the third ventricle, tanycytes act as neural stem cells supporting this continuous neurogenesis process. In sheep, a large long-lived mammalian model, we have recently shown that the hypothalamic neurogenic niche harbours adult neural stem cells (NSCs), the tanycytes, capable of generating new neurons and glial cells. In this seasonal species, the function of reproduction is limited to one period of the year and the timing of this restricted sexual activity period is driven by the photoperiod and the pineal hormone, melatonin. We have shown a seasonal peak in hypothalamic cell proliferation rates occurring around 55 days after the onset of the sexual activity period, concomitant to an increase in the expression of doublecortin, a marker expressed in young migrating neurons, indicating a simultaneous enhancement of the rate of neurogenesis. We provided evidence that this peak of neurogenesis is pineal dependent, suggesting a regulatory role for melatonin in this process. Furthermore, the disruption of hypothalamic neurogenesis following the administration of the antimitotic cytosine-b-D-arabinofuranoside (Ara-C) leads to an alteration of the timing of reproduction. Together, our results correlate the cyclic increase of hypothalamic neurogenesis to seasonal reproduction and suggest that the photoperiod-regulated hypothalamic neurogenesis plays a role in the seasonal reproductive physiology.