Project/Area Number |
11671389
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | JUNTENDO UNIVERSITY |
Principal Investigator |
MIYAJIMA Masakazu Juntendo University, School of Medicine, Assistant Professor, 医学部, 講師 (60200177)
|
Co-Investigator(Kenkyū-buntansha) |
ARAI Hajime Juntendo University, School of Medicine, Associate Professor, 医学部, 助教授 (70167229)
SATO Kiyoshi Juntendo University, School of Medicine, Professor, 医学部, 教授 (10112707)
菱井 誠人 順天堂大学, 医学部, 講師 (40189783)
|
Project Period (FY) |
1999 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | HTX Rat / DNA microarray / Astrocyte / Aquaporin 4 / C type natriuretic peptide / C type natriuretic peptide / 先天性水頭症ラットHTX / cDNAアレイ / RT-PCR / voltage-gated sodium channel aquaporin4 / 免疫組織染色 / ラット / 神経細胞 / cDNA expression array / voltage-gated sodium channel |
Research Abstract |
We used adult compensated hydrocephalic HTx rats as the experimental animal. Using a DNA microarray technique, we screened genes with decreased or increased expression in the cerebral cortex of rats with compensated hydrocephalus by comparing genes expressed hi the normal rats and those expressed in the compensated hydrocephalus. The expression of 12 genes was found to be downregulated, while 12 genes were upregulated. We focused our attention on water channel aquaporin-4, which has been reported to play an important role hi the transport of water hi the central nervous system. It has been confirmed by RT-PCR that expression of aquaporin4 is more pronounced hi the cerebral cortex of hydrocephalic HTx rats than hi the cerebral cortex of normal rats. Aquaporin-4 is mainly present hi ependymal cells and the perivascular astrocyte foot process. It has been reported to be associated with transport of water at these sites. Expression of aquaporin-4 was more pronounced hi ependymal cells of h
… More
ydrocephalic HTX rats than hi those of normal rats. Likewise, expression of aquaporin-4 was more pronounced around the vessels of the cerebral cortex of hydrocephalic HTX rats than around those of normal rats. Considering this and the fact that aquaporin-4 plays an important role hi the transport of water, it may be surmised that the increase in expression of aquaporin-4 in the hydrocephalic cerebrum is involved in the development of an alternative pathway for the circulation of cerebro-spinal fluid. Furthermore, if expression of aquaporin-4 can be artificially increased, it could become a new treatment for hydrocephalus by promoting the development of an alternative pathway for cerebro-spinal fluid circulation. Previously, we focused our attention on C-type natriuretic peptides and reported that intracranial pressure could be lowered by injecting them into the lateral ventricle, but the mechanism was unidentified. We fixed the glioma cell line U373, which has a CNP receptor, after cultivation for three days in a medium containing 1 micro mol CNP. Immunostaining using an aquaporin-4 antibody showed that expression of aquaporin-4 was markedly increased in cells cultivated with CNP relative to cells cultivated in a medium without CNP. Likewise, expression of aquaporin-4 was markedly increased hi astrocytes cultivated hi a medium containing CNP relative to control. Less
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