Evaluation of Kiss1 and Fezf1 neurons functions in adult hypothalamic neurogenesis triggered by hormones and nutritional stimuli

Abstract

The hypothalamus integrates central and peripheral signals to control many autonomic functions, such as energy balance and reproduction. This regulation occurs synchronously since the metabolic state determines several behavioral and physiological adaptations to ensure the reproductive success of the species. As a protective mechanism, neurogenesis in the hypothalamus is preserved until adulthood and results from synergistic actions of multiple stimuli, such as neurotrophic factors, hormones, and nutrients. The Brain-Derived Neurotrophic Factor (BDNF) has been widely studied due to its involvement in neurogenesis and the regulation of energy homeostasis. From a published single-cell sequence analysis (single-cell RNAseq), we have identified, in the arcuate nucleus of the hypothalamus (ARC), only two neuronal populations expressing BDNF: kisspeptin (Kiss1) and zinc finger 1 (Fez1). Kiss1 neurons participate primarily in the control of reproduction and are also involved in the regulation of the energy balance through projections with AgRP and POMC neurons. Fezf1 neurons, in turn, are essential for the development of the olfactory system, and also modulate reproductive behavior. From the identification that only Kiss1 and Fezf1 neurons produce BDNF in the ARC, in this project we will investigate through which mechanisms both are involved in hypothalamic adult neurogenesis triggered by hormonal and nutritional stimuli. To achieve this aim, we will (1) characterize the distribution of these neurons in the hypothalamus; (2) map which cells communicate with these two neuronal populations, to trace the migration route of the neural precursors of the third ventricle into different regions of the hypothalamic parenchyma; (3) determine which hormonal and nutritional stimuli Kiss1 and Fezf1 triggers BDNF production, thus increasing adult neurogenesis; and (4) evaluate the impact of selective deletion of BDNF in each of these neuronal subpopulations on hypothalamic adult neurogenesis in response to the same hormonal and nutritional stimuli. Data obtained from this project will highlight Kiss1 and Fezf1 neurons as new targets of interest in studies involving adult hypothalamic neurogenesis. (AU)