Project/Area Number |
04454256
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Neurology
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
TATEISHI Jun Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (70033305)
|
Co-Investigator(Kenkyū-buntansha) |
KITAMOTO Tetsuyuki Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (20192560)
|
Project Period (FY) |
1992 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥5,300,000 (Direct Cost: ¥5,300,000)
|
Keywords | Creutzfeldt-Jakob / prion protein / follicular dendritic cell |
Research Abstract |
Creutzfeldt-Jakob disease (CDJ), Gerstmann-Straussler syndrome (GSS) and scrapie are transmissible neurodegenerative diseases. Attempts to purify the scrapie agent have led to the descovery of a glycoprotein designated prion protein (PrP). The proteinase-resistant isoform of PrP named PrPCJD or PrPSc has been implicated as a main component of the infectious agent of scrapie and DJD.Both the replication of the agent and the accumulation of PrPSc occur in the lymphoreticular system, notably in the spleen, long gefore the involvement of the central nervous system. The follicular dendritic cell (FDC), a major antigen-presenting cell in the lymphoid tissue, is the site of accumulation of PrPCJD in the lymphoreticular system of mice infected by the CDJ agent passed serially in mice. The accumulation of PrPCJD in FDCs has been observed in the spleen within 30 days after inoculation of the agent whether via the intracerebral or the intraperitoneal route and does not depend on the agent strain. However, the ccumulation of PrPCJD in FDCs does not occur in mice inoculated with human CDJ or GSS materials (first-passage mice), whereas it always occurs in mice inoculated with the CJD agent once it has been adapted to the mouse. These phenomena may thus suggest an intense expression of the species barrier in the lymphoreticular system. Further significance of the species barrier in the lymphoreticular system might be suggested by our data as follows : the SCID mouse is the only strain in which PrPCJD did not accumulate in FDCs after inoculation of the mouse-adapted CJD strain ; in addition, transmission of this CJD strain to the SCID mouse via the intraperitoneal route was unsuccessful whereas that via the intracerebral route was successful. These data suggest the possibility that the accumulation of PrPCJD in FDCs is an essential step for the intraperitoneal- inoculated CJD agent to invade the central nervous system.
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