2010 Fiscal Year Final Research Report
The role of PEDF in injured brain
| Project/Area Number |
20590089
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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 |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
YABE Takeshi Kitasato University, 大学院・感染制御科学府, 講師 (40239835)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Haruki 北里大学, 大学院・感染制御科学府, 教授 (60096691)
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| Project Period (FY) |
2008 – 2010
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| Keywords | PEDF / グリア細胞 / グルタミン酸毒性 / 神経保護作用 / 脳虚血 |
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| Research Abstract |
Pigment epithelium-derived factor (PEDF) is a 50-kDa glycoprotein that protects various types of cultured neurons against neurotoxic stimuli, but its precise role in the CNS is not fully elucidated. In this study, we used rats whose brains were transfected to over-express human PEDF in order to elucidate the neuroprotective effect of PEDF following transient middle cerebral artery occlusion (MCAO). A replication-defective adenoviral vector containing the human PEDF gene (Ad.PEDF) or E. coliss-galactosidase (Ad.LacZ) was directly injected into the right striatum at 7 days prior to 70 min of MCAO in rats. Infarct volume and degree of edema of the Ad.PEDF-treated group were significantly reduced compared to the Ad.LacZ-treated group 24 h after MCAO. Degeneration of neurons, astrocytes, and oligodendrocytes caused by MCAO were attenuated by over-expression of PEDF. The up-regulation of certain pro-inflammatory genes and water channel aquaporin 4 after MCAO was significantly reduced in Ad.PEDF-injected striatum. In conclusion, the results from this study provide the first in vivo evidence that PEDF is effective in protecting CNS neurons from ischemic insult, suggesting that PEDF may have a role as an endogenous neuroprotectant in the CNS.
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[Journal Article] PEDF up-regulation induced by memantine, an NMDA receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells.2010
Author(s)
Namba T, Yabe T, Gonda Y, Ichikawa N, Sanagi T, Arikawa-Hirasawa E, Mochizuki H, Kohsaka S, Uchino S.
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Journal Title
Neuroscience 167
Pages: 372-383
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[Journal Article] Inhibition of nuclear translocation of apoptosis-inducing factor is an essential mechanism of the neuroprotective activity of pigment epithelium-derived factor in a rat model of retinal degeneration.2008
Author(s)
Murakami Y, Ikeda Y, Yonemitsu Y, Onimaru M, Nakagawa K, Kohno R, Miyazaki M, Hisatomi T, Nakamura M, Yabe T, Hasegawa M, Ishibashi T, Sueishi K.
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Journal Title
Am.J.Pathol. 173(5)
Pages: 1326-1338
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[Journal Article] Protective role of reactive astrocytes in brain ischemia.2008
Author(s)
Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Stahlberg A, Aprico K, Larsson K, Yabe T, Moons L, Fotheringham A, Davies I, Carmeliet P, Schwartz JP, Pekna M, Kubista M, Blomstrand F, Maragakis N, Nilsson M, Pekny M.
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Journal Title
J.Cereb.Blood.Flow.Metab. 28(3)
Pages: 468-481
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