Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish

Abstract

Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis.Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed.

Three nuclear and two membrane estrogen receptors in basal teleosts, Anguilla sp.: Identification, evolutionary history and differential expression regulation

“…Estradiol reaches the brain after peripheral secretion by the gonads, but it may also be locally produced via brain steroidogenesis (for review: Coumailleau et al, 2015). In teleosts, besides exerting feedback regulatory effects on the activity of the brain-pituitary gonadotrope axis, one major role of estradiol is the regulation of neurogenesis by glial cells (Lin et al, 2015;Nagarajan et al, 2013;Pellegrini et al, 2015;Xing et al, 2014). Previous data in eels indicated that estradiol exerts a positive feedback on mGnRH (mammalian GnRH) expression by anterior brain neurons and also on brain aromatase expression by glial cells Montero et al, 1995).…”

Neuroendocrine disruption of organizational and activational hormone programming in poikilothermic vertebrates

“…In European sea bass (Dicentrarchus labrax) , males generally display higher brain aromatase activity than females (Gonzalez and Piferrer 2003). In teleost, radial glial cells (RGC), are the exclusive site of cyp19a1b expression (Pellegrini et al 2016), which raises the intriguing question of how RGC signal to adjacent neurons via estrogens. Both estrogens and androgens (aromatizable and non-aromatizable) increase GnRH (Breton and Sambroni 1996, Dubois et al 1998), but it is unclear if this is direct or indirect, since the expression of ER in GnRH neurons remains controversial.…”

“…Both estrogens and androgens (aromatizable and non-aromatizable) increase GnRH (Breton and Sambroni 1996, Dubois et al 1998), but it is unclear if this is direct or indirect, since the expression of ER in GnRH neurons remains controversial. Numerous other neurons express nuclear and membrane ER, so both local estrogen from RGC, and peripheral estrogens could differentially affect central neuronendocrine systems (Pellegrini et al 2016; Xing et al 2014). Chronic deprivation of estrogens via aromatase inhibition with fadrozole in adult female goldfish revealed that numerous hypothalamic genes were affected: these included calmodulin, activin-βA, and ornithine decarboxylase 1 (Zhang et al 2009b).…”

“…In mammals and birds, sex steroids are important for organizational and activational effects on the brain (Diotel et al 2011b; Pellegrini et al 2016; do Rego and Vaudry 2016). In fish, there are many examples of activational effects by sex steroids, but organizational events due to these hormones are more difficult to ascertain due to their high brain plasticity.…”

“…Neurosteroid biosynthesis occurs in RGC (Xing et al 2014; Pellegrini et al 2016); the exclusive site for brain aromatase activity in teleosts. The mRNA for steroidogenic acute regulatory protein ( star) , responsible for shuttling cholesterol into the mitochondria), as well as mRNA for steroidogenic enzymes cyp17a1 and hsd3b , involved in key biosynthetic steps of neurosteroids, were sequenced from cultured RGCs (Xing et al 2014).…”