| Project/Area Number |
04454257
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Gifu Pharmaceutical University |
|---|
Principal Investigator |
HAYASHI Kyozo Gifu Pharmaceutical University, Department of Molecular Biology, Professor, 薬学部, 教授 (00029935)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Yoshiko Gifu Pharmaceutical University, Department of Molecular Biology, Associate, 薬学部, 助手 (20219108)
FURUKAWA Shoei Gifu Pharmaceutical University, Department of Molecular Biology, Associate Profe, 薬学部, 助教授 (90159129)
NISHITANI Hiroshi National Utano Hospital, President, 宇多野病院, 院長
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
|
|---|
| Keywords | neurotrophic factor / Alzheimer's disease / coenzyme / nerve growth factor (NGF) / enzyme immunoassay (EIA) / astrocytes / forebrain-lesioned rat / NGF synthesis stimulation / interleukin / EIA / 神経成長因子(NGF) / Alzheimer型老人痴呆症 / 糖鎖 / コリンアセチルトランスフェラーゼ(CAT) / 生合成 / 制御機構 / アストログリア細胞 |
|---|
| Research Abstract |
(1)The coenzymes such as pyrroloquinoline quinone, lipoic acid, found to have the stimulatory effect of NGF synthesis without causing cytotoxicity. Especially, pyrroloquinoline quinone showed strong activity of pormoting NGF synthesis in mouse astrocytes, whereas lipoic acid has the stong effect on BALB c/3T3 cells.
(2)6-(4-Hydroxybuty1)-2,3,5-trimethy1-1,4-benzoquinone (TMQ) stimulated NGF synthesis in astrocytes. The compound showeds improving effects on memory and choline acetyltransferase (CAT) activity in basal forebrain-lesioned rats, an amnesia animal model. TMQ ameliorated amnesia in the water maze and passive avoidance tanks. This compound not only restored the reduced CAT activity in the parietal cerebral cortex, but also increased NGF content and CAT activity in the hippocampus.
(3)The NGF level using our enzyme immunoassay system for human NGF were found to be no difference in NGF level in serum, brain-spiral fliud, or brain (hippocampus and parietal cortex) obatained from no
… More
rmal people and patients with Alzheimer's disease.
(4)In the stimulatory effect of alkylcatechols on NGF synthesis, neither PKC-dependent pathway nor cAMP-dependent pathway was dominant.
(5)Interleukin (IL)-2 supported the servival and enhanced neurite extention of cultured hippocampal neurons prepared from embryonic 18-day-old rats. IL-2 also supported the survival of cultured cortical, striatal, and septal ieurons. These results indicate that IL-2 has a survival-promoting effect on a wide variety of neurons.
(6)IL-4 and IL-5 singifiantly increased the amounts of NGF secreted by mouse astrocytes, whereas IL-2, IL-3, and IL-6 had no significant effect. IL-4 and IL-5 showed marked increases in NGFmRNA levels in astrocytes as demonstrated by the reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of IL-4 and IL-5 was greater in quiescent astrocytes than in growing cells.
(7)Denervation of depaminergic neurons by intra nigra injection of 6-hydroxydopamine (6-OHDA) increased NGF content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. Less
|
