Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH) neurons

Abstract

Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

Dopamine receptor agonist bromocriptine restrains the follicular development, hatchling success and puberty in Gambusia affinis

“…In teleosts, GnRH1 peptide is having hypophysiotropic nature, as shown by the axonal projections of GnRH secreting neurons of POA into the pituitary gland through hypothalamo-hypophysial tract (Karigo & Oka, 2013). Moreover, the antibody employed in the present study was shown to label hypothalamic GnRH neurons of preoptic region in the zebrafish D. rerio (Cortes-Campos, Letelier, Ceriani, & Whitlock, 2015). Therefore, the GnRH immunoreactivity observed in the pituitary gland suggests that the antibody employed in the present study labeled GnRH1 neurons in G. affinis.…”

Exosomal 2′,3′-CNP from mesenchymal stem cells promotes hippocampus CA1 neurogenesis/neuritogenesis and contributes to rescue of cognition/learning deficiencies of damaged brain

“…For spheres in all the three groups, we observed that most cells in the spheres expressed Nestin and only a few sphere cells expressed GFAP (Figure S1B). The characteristics of these spheres correspond with that of neurospheres described in the literature …”

“…The characteristics of these spheres correspond with that of neurospheres described in the literature. [48][49][50][51][52][53]…”

Androgen induced cellular proliferation, neurogenesis, and generation of GnRH3 neurons in the brain of mature female Mozambique tilapia

“…Cortés-Campos et al . 43 demonstrated that adult zebrafish-derived hypothalamic neurospheres generate GnRH neurons, including GnRH3 ones. They also demonstrated that the number of GnRH neurons increased following exposure to testosterone or GnRH3.…”