| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Pieces of mesencephalic and medullary raphe tissues were transplanted into the cerebella of 5,6 DHT-treated adults rats. The extent of axonal outgrowth of serotonergic and dopaminergic neurons in the grafts was immunohistochemically studied. The outgrowing serotonergic fibers from the mesencephalic raphe graft showed a hyperinnervation pattern in the cerebellar cortex adjacent to the graft. Furthermore, a glomerulus-like accumulation of serotonergic fibers was observed in the granular layer. In the cases of medullary raphe grafts, the relatively abundant outgrowing serotonergic fibers showed a laminar organization in the cerebellar cortex near the graft, which was similar to the normal distributional pattern. These results indicate that serotonergic and dopaminergic neurons located within the mesencephalic raphe graft clearly differed from each other in their ability to extend their processes into the host cerebellum, which provides further evidence for the existence of specific interactions between outgrowing serotonergic fibers and their terminal fiber targets. The homozygote (Pdn/Pdn) of the mutant mouse showed several brain abnormalities, and a significant decrease of S-100beta. In order to clarify the effects of the retarded production of S-100beta on the development of monoaminergic neuron system, immunocytochemical studies of TH, 5-HT, S-100beta and GFAP, and HPLC study for 5-HT and 5-HIAA of Pdn/Pdn mouse were examined, the results were compared with the control. In both animals, S-100beta positive cells and serotonergic fibers were widely distributed throughout the brain. however, hippocampus and caudo-dorsal cortex of Pdn/Pdn mouse were markedly reduced in S-100beta positive cells and serotonergic fibers. Abnormal distribution of GFAP positive fibers was also observed in the neocortex and hippocampus. These results suggest that S-100beta is a serotonergic growth factor, and this mutant mouse is a useful model to study neuro-glial neurotrophic interactions.
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