1999 Fiscal Year Final Research Report Summary
Analytical study on the role of platelet-derived growth factor in developing and ischemic brain.
| Project/Area Number |
10670200
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Toyama Medical and Pharmaceutical University (1999)
Shiga University of Medical Science (1998) |
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Principal Investigator |
SASAHARA Masakiyo Faculty of Medicine, Toyama Medical and Pharmaceutical University professor., 医学部, 教授 (20154015)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Platelet-derived growth factor / Heparin-binding epidermal growth factor / ischemia / development / brain / kidney / regeneration / neurotrophic factor |
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| Research Abstract |
Current project was conducted to know the role of platelet-derived growth factor (PDGF) B-chain in either developing brain or brain subjected to injury.
(1) We identified two PDGF-B mRNAs (3.5 and 2.6 kb) expressed in normal rat brain. It was found that the mRNA of 2.6 kb was a truncated form of that of 3.5 kb, and that truncated form of the gene is crucial for PDGF-B translation in the neuron during development or at a acute phase of ischemia of the brain.
(2) In hypoxic / ischemic encephalopathy of neonatal rat brain, PDGF-B and β-receptor expression was induced in the neurons surrounding infarction. This fact revealed PDGF-B/β-receptor system plays a role in the survival of neurons in neonatal rat brain.
(3) Regenerating renal tubular epithelial cells expressed both PDGF-B and β-receptor after ischemia/reperfusion insult. Inhibitors of PDGF-B, trapidil and Ki6896, prohibited recovery of renal function and suppressed epithelial regeneration. PDGF-B is important for the regeneration of renal tubular epithelial cells after acute injury.
(4) Neuronal expression of PDGF-B disappeared prior to apoptotic neuronal death selectively in CA 1 lesion of hippocampus after transient forebrain ischemia, and in retinal ganglion cells after transection of optic nerve. PDGF-B is important for the survival of neurons.
(5) Currently, we are testing the function of PDGF-B in neonatal rat brain by introducing anti-sense oligonucleotide, and are getting results to show the importance of PDGF-B in the normal maturation of the brain (unpublished data).
(6) We have found that Heparin-binding epidermal growth factor is widely expressed in the brain, and is upregulated in neonate and in the brain after ischemia. Function as a ligand for EGF receptor is suspected in the brain.
(7) We reported mutation in the microtubule-associated protein tau in a patient of pallido-nigra-luysian degeneration.
(8) We detected mossy fiber sprout in the hippocampus of rat with hereditary epilepsy.
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[Publications] Yasuda M, Kawamata T, Komure O, Kuno S, D'Souza I, Poorkaj P, Kawai J, Tanimukai S, Yamamoto Y, Hasegawa H, Sasahara M, Hazama F: "Schellenberg GD, Tanaka C. A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration."Neurology. 11 : 53 (4). 864-868 (1999)
Description
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