Role of aromatase and radial glial cells in neurotoxin-induced dopamine neuron degeneration and regeneration.

Radial glial cells (RGCs) in teleost brain are progenitor cells that express aromatase B and produce estrogens. Controversial data suggest that estrogens are critical for brain repair and neurogenesis in teleosts. Using a goldfish model for neurotoxin-induced Parkinson-like syndrome, we investigated the possible roles of RGCs, especially estrogen synthetic function, in the processes underlying dopamine neuron regeneration. The data indicate that dopamine neuron degeneration and aromatase activity inhibition could be respectively achieved in vivo with treatments with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) and fadrozole in female goldfish. The expression of genes in the telencephalon and hypothalamus related to RGC functions including gfap, gdnf and bdnf as well as genes related to mature dopamine neuron functions including th, slc6a3 and pitx3 are under modulation of estrogens. Together these results revealed that the activation of radial glial cells and dopamine neuron recovery after MPTP insult is aromatase-dependent. Findings in this study provide support for the hypothesis that endogenous estrogens are neuroprotective in goldfish. Future studies focus on the molecular pathways for enhancing protective functions of estrogens and understanding global effects of estrogens in the central nervous system.