Neurotrophic factor for serotonergic neurons prevents degeneration of grafted raphe neurons in the cerebellum

Earlier studies in this laboratory have shown that partial serotonergic (5-HT) deafferentation from the hippocampus induced a homotypic sprouting. The 5-HT-denervated hippocampus was further found to be a favorable environment for the growth of grafted 5-HT, but not for norepinephrinergic neurons. In the current study, we have extracted a trophic factor in the denervated hippocampus with hypotonic solution in high-speed supernatant fraction. The trophic extract was assayed in a unique experimental paradigm--test the growth of grafted 5-HT neurons in the cerebellum, which receives the least 5-HT innervation, and where grafted 5-HT neurons have seldom survived. The diluted trophic extract (1:200) produced a dramatic increase in (a) the survival rate, (b) the 5-HT fiber-density, and (c) the 5-HT and 5-hydroxyindoleacetic acid levels of grafted 5-HT neurons in the cerebellum. In addition, Nissl-counterstaining showed that the size of the grafted raphe also apparently increased. The concentrated trophic extract (1:1) did not increase the survival rate of the grafted raphe neurons. These results indicate that (a) the supernatant in the 5-HT-denervated hippocampus contains a potent neurotrophic factor to 5-HT neurons (b) which can either directly or indirectly also support non-5-HT raphe neurons, and (c) possibly an inhibitory factor is present which is detrimental to 5-HT neurons in high concentration.