Neurogenesis, Aromatase and Œstradiol
We study the functions of estrogens in the developing, adult and regenerating zebrafish brain. We use a variety of approaches to understand the mechanisms underlying estrogen synthesis in the brain and the response of neural stem cells to estrogen signalling.
The rationale for using zebrafish is that :
Fish are the champions of adult neurogenesis :
In mammals, significant neurogenesis occurs in two discrete regions of the adult mammalian brain. In those two regions new neurons are generated from a resident population of neural progenitor cells that are maintained throughout adult life.
In contrast, the brain of fish has a much more pronounced capacity to grow during adulthood due to the presence of mitogenic zones capable of generating new neurons in many parts of the regions of the brain. This suggests that the brain of fish presents a highly permissive environment allowing persistence and proliferation of progenitors in adult fish. Our work aims at exploring the intrinsic and extrinsic factors establishing a permissive environment and allowing maintenance of neural stem cell proliferation and active neurogenesis in the brain of fish.
The brain of fish has an exceptional capacity to produce estrogens
It is well known that the brain of fish has a high aromatase activity. Aromatase is the enzyme that converts androgens (such as testosterone) into estrogens such as estradiol.
Estrogens are produced in progenitor cells of the adult fish brain :
We and others have recently shown that aromatase, the estrogen synthesizing enzyme, is expressed in radial glial cells. We have also shown that radial glial cells are progenitors in the brain of adult zebrafish
Our hypothesis is that estradiol could participate in maintaining a permissive environment in the brain of adult fish.
This hypothesis is based on the fact that increased estrogen production has recently been reported in several situations of embryonic neurogenesis or the brain of mammals and birds after mechanical or chemical injury. Thus, it is possible that fish presents an exaggerated situation of a more general mechanisms involving estrogens in embryonic, adult or reparative neurogenesis
Perspectives
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.
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