| Project/Area Number |
10470093
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hygiene
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
SAITO Takeshi Hokkaido Univ., School of Med., Asso. Pro., 医学部, 助教授 (40153811)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HATA Akira Asahikawa Med. College, Pro., 医学部, 教授 (00244541)
HOSOKAWA Toshiyuki Hokkaido Univ., Center for Res. Develop. Higher Edu., Asso. Pro., 高等教育機能開発総合センター, 助教授 (00157025)
TAKAHASHI Kyoko Hokkaido Univ., School of Med., Inst., 医学部, 助手 (50292008)
KURASAKI Masaaki Hokkaido Univ., School of Med., Asso. Pro., 大学院・地球環境科学研究科, 助手 (80161727)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥8,300,000 (Direct Cost: ¥8,300,000)
|
|---|
| Keywords | metal ion transporter / ATP7B / Copper / CNS / Neurological function / metabolism of trace elements |
|---|
| Research Abstract |
In the present study, we intended to evaluate the mechanism of membrane transport of metal ions in the central nervous system and its relation to the brain function. Results obtained in the present investigations are as follows;
1. Localization of copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain, kidney, small intestine and liver of the Long-Evans agouti rat using immunohistochemical technique. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brain stem of the rat brain, the cortex and the outer stripe of the outer medulla in the kidney, Paneth cells of the small intestine, and hepatocytes. ATP7B was observed predominantly in the regions in which high amounts of copper and copper-binding proteins such as Cu-ZnSOD and metallothionein and NO synthase were detected. Thus, in normal tissue, ATP7B was considered to regulate not only copper homeostasis and biosynthesis of holo copper-binding proteins but also NO synthesis in CNS.
2.. Changes in concentrations of trace elements and neurotransmitters by aging were determined in the brain of Senescence-Accelerated Mouse P10(SAMP10), which showed brain atrophy and deficits in learning and memory. Zn, Cu and Mn concentrations in most regions of SAM-P10, were significantly lower than those in the control rat. Mo concentration in the brain of SAM-P10 was significantly higher than that in the control. The excess amount of glutamate and glycine release from the hippocampal CA3 regions of SAM-P10 aged 12 months was observed as compared to that in the control. These results suggest that abnormal membrane transports of metal ions in CNS induce senescence-acceleration of the brain of SAMP10.
|
