Physiopathology of the adult hypothalamic neurogenic niche – HypNeurogen

In adulthood, some areas of the brain of mammals, including humans, retain a renewal capacity supported by the maintenance of several populations of neural stem cells which continuously produce new neurons. A thorough knowledge of this striking case of structural plasticity in the mature brain should open a wide range of therapeutic prospects and will be an asset for the development of the effective transplantation of neural stem cells in the brain to compensate for the deficiencies caused by many neurological diseases.
Several recent studies in rodents have shown that the hypothalamus, a brain structure that plays a key role in the neuroendocrine regulations of the body (metabolism, food intake, reproduction, thermoregulation...) houses neural stem cells in neurogenic niches located in different hypothalamic subnuclei. Data regarding the existence of such a neurogenic niche in the hypothalamus of the adult human brain are very limited.
We recently showed the existence of a neurogenic niche in the mature hypothalamus of sheep, a long-living mammalian model and we found a comparable expression pattern of stem cell markers in the adult human hypothalamus, suggesting a similarity in the organization of this neurogenic niche in both species.
Based on our previous work and on our preliminary data, the objective of the HypNeurogen proposal is to validate the hypothesis of the existence of neurogenic niches in the adult human hypothalamus, and thanks to the opportunity to efficiently manipulate the hypothalamic neurogenesis in the sheep, we intend to develop in vivo some non-invasive longitudinal imaging techniques which, when applied to human, will allow us to assess the role of the new hypothalamic neurons in physiology and metabolic pathology.
HypNeurogen has the ambition to develop innovative and integrated approaches using mass spectrometry, electron microscopy and the latest developments in neuroimaging techniques to identify factors capable of stimulating the hypothalamic neurogenesis, to reconstruct and compare the cytoarchitecture of neurogenic niches in sheep and humans, to analyze the migratory potential of the newly formed neurons in the hypothalamus, to detect neurogenesis in vivo through longitudinal studies, and finally to understand the contribution of hypothalamic neurogenesis in human pathologies related to neurological dysfunctions of food intake. In humans this innovative approach will bring new insights about the role of the production of new hypothalamic neurons in normal and pathological contexts.