The NAO team studies four main topics:
The functions of steroids, notably estrogens and progesterone, on adult neurogenesis in the brain of zebrafish.
We study both embryonic and adult neurogenesis. We also look into the mechanisms underlying brain repair in a model of mechanical lesion developed in the lab. The rationale for using zebrafish is that:
- fish are the champions of adult neurogenesis
- the brain of fish has an exceptional capacity to produce neurosteroids
- neurosteroids are produced in brain stem cells, i.e. radial glial cells
Understanding the role of estrogens in the regulation of neurogenesis in the normal or injured adult brain represents hopes of new therapeutic procedures at aiming stimulating the processes of endogenous neurogenesis.
The synthesis of neurosteroids and the steroid targets in the brain of zebrafish
In vertebrates, the brain is well known for being a target for blood-borne peripheral steroid hormones or for steroids produced locally from peripheral precursors. The hypothesis that steroids can be produced entirely within the brain was first raised in the early 80s, and documented for pregnenolone and dehydroepiandrosterone (DHEA). This prompted the development of an active research field aiming at better understanding the capacity of the brain to produce steroids and the functions of these so-called “neurosteroids”. In mammals, it is now recognized that a variety of steroids, including sex steroids, can be produced from cholesterol in certain brain regions. This part of our project examines the sites of expression of the steroidogenic enzymes in the brain of zebrafish. We also study the sites of expression of steroid nuclear and membrane receptors .
The central control of reproduction in the brain of teleosts.
We mainly focus on the GnRH and Kisspeptins systems and their interactions. These two neuropeptides play central roles in the control of reproductive functions. We also look at the effects of steroids, mainly estrogens, on these neuroendocrine circuits. Such studies are interesting on an evolutive point of view by looking at how the mechanisms controlling reproduction have emerged from invertebrates and evolved in vertebrates.
This research also permits to better understand the mechanisms controlling reproduction in captive fish, leading to improve technologies to control puberty and sexual maturation. This work is supported by the European Union, notably the LIFECYCLE project (http://www.lifecycle-fp7.eu/).
The effects of Endocrine Disrupting Chemicals (EDCs) on neurogenesis and the neuroendocrine circuits
Fishes in general have already shown their usefulness for the evaluation of the effects of environmental contaminants in real world conditions. In our lab, we study the effects of endocrine disrupting chemicals (EDCs) on neurogenesis and the neuroendocrine circuits. We also aim at developing techniques that permit to identify such chemicals in vivo and in vitro. We have characterized the cyp19a1b gene as an outstanding biomarker of zenoestrogen exposure and we have developed in vivo and in vitro screening tests permitting to screen chemicals of complex mixtures for estrogenic activities. It is important to mention that the OECD selected embryos of fishes and amphibians as potential alternatives that permit screening early EDC effects in vertebrate models.