Serotonin is one of several neurotransmitters which have been established as neuronal-growth regulating substances. As such, serotonin facilitates development in the immature brain, and promotes plasticity in the adult brain. Since a lack of trophic substances has been suggested to play a role in brain aging and age-related diseases, it is likely that serotonergic mechanisms could be important here as well. One mechanism by which serotonin functions as a trophic agent, is by an action on 5-HT1a receptors on astroglial cells. These receptors can stimulate the release of a cortical and serotonergic trophic factor - S-100beta. In recent studies of Alzheimer's Disease, changes in serotonin terminal density, in 5-HT1a receptor number and levels of S-100beta have all been reported. It is clear that an understanding of the factors regulating 5- HT1a receptor release of S-100beta is important to understanding brain aging. The proposed research will study 5-HT1a receptors and S-100beta release in four tissue culture models of astroglial cells, representing different developmental stages. The number of receptors will be studied by autoradiography, using the specific 5-HT1a receptor label 3H-8-OH-DPAT. The amount of S-100beta released, and within the cells, will be determined by radioimmunoassay. The ability of other neurotransmitters and neuromodulators to affect receptor number or S-100beta release will also be studied. Finally, the results derived from tissue culture will be extended into whole animal studies and into post-mortem human tissue.
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