| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Previously, we found platelet-derived growth factor-B chain (PDGF-B) and its receptor expression in monkey brain. Here, in this project, we demonstrated, 1) PDGF-B expression in normal rat brain : In normal and mature rat brain, we have determined the localization of PDGF-B gene in neurons by in situ hybridization histochemistry. These transcripts were almost 3.5 and 2.6 kb, as shown by northern blot. The protein expression was confirmed by the detection of PDGF-B-related mitogenic activity in the brain. 2) Regulation of PDGF-B expression related to cerebral insults and transplantation : Rapid and transient increase of PDGF-B expression was induced in the neurons in the vicinity of the lesions, such as focal cerebral ischemia and hypoxic/ischemic injury. In the transplantation study of rat olfactory bulb, PDGF-B expression was observed in a close proximity to the radiation of individual axon from olfactory nerve bundles to surrounding neuropil. These findings obtained in cerebral injur
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ies and transplantation model suggest that PDGF-B should play a role in the protection of neurons at risk, and in the remodeling of neural fiber network, together with previously demonstrated its neurotrophic activity to cultured neuronal cells. Following focal cerebral ischemia, transient PDGF-B upregulation was followed by increase of PDGF-b receptor expression in cells such as neurons, reactive glial cells and macrophages. After cerebral stab wound, the expression of PDGF-B in macrophages correlated with reactive astrogliosis.These results obtained in focal ischemic injury and stab wound further suggest the role of PDGF-B in the healing process of the injured brain. 3) Cloning of the PDGF-B gene from brain : Immediately after focal cerebral ischemia, rapid induction of PDGF-B gene of short form was observed. We successfully cloned its gene from brain by use of anchored PCR cloning. Long untranslated 5'-end sequence of PDGF-B gene has been shown to inhibit its protein translation. In the present study, short transcripts which increased after cerebral injury was determined as truncated form, lacking their 5'-end untranslated sequence. Novel regulatory mechanism of protein expression was demonstrated, that is, induced truncated gene expression, lacking translation inhibitory sequence in 5'-end untranslated region, supply template for PDGF-B protein translation. 4) In summary, we have determined PDGF-B gene expression in neurons and its expression related to insults and transplantation. Further, gene cloning from brain demonstrated novel regulatory mechanism for the protein expression. Less
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