Grant-in-Aid for Scientific Research (B).
|Section||Joint Research .|
|Research Institution||Nagoya City University|
NISHINO Hitoo Professor Department of Physiology, Nagoya City University Medical School, 医学部, 教授 (60073730)
サンバーグ ポール 南フロリダ大学, 医学部, 教授
ボーロンガン セサリオ 国立保健研究機構, 研究員
INUBUSHI Toshiro Professor, Molecular Neurobiology Research Center, Shiga University of Medical Science, 分子神経生物学研究センター, 教授 (20213142)
FUKUDA Atsuo Professor Department of Physiology, Hamamatsu Medical School, 医学部, 教授 (50254272)
HIDA Hideki Department of Physiology, Nagoya City University Medical School, 医学部, 助手 (00305525)
CESARIO V. Borlongan 国立保健研究機構, 研究員
MORIKAWA Shigehiro Associate Professor, Molecular Neurobiology Research Center, Shiga University of Medical Science (60220042)
BORLONGAN Cesario v. Visiting Associate, Cellular Neurophysiology Section, national Institute on Drug Abuse
|Project Fiscal Year
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥4,400,000 (Direct Cost : ¥4,400,000)
Fiscal Year 1999 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1998 : ¥2,400,000 (Direct Cost : ¥2,400,000)
|Keywords||mitochondrial toxin / cell death / necrosis / lateral striatal / NO / neural transplantation / ミトコンドリア / 細胞死 / ネクローシス / 外側線条体 / 神経移植 / アポトーシス / 外側線条体動脈 / ミトコンドリア毒 / 神経毒 / 機能再建|
Systemic administration of 3-nitropropionic acid (3-NPA, 20 mg/kg, s.c., daily, 2 or 3 days) to rats induced striatum selective lesions, and animals manifested motor symptoms. In the present study, we analyzed the mechanisms of the striatal vulnerability and tried to protect the damage.
Results are as follows.
1. 3-NPA intoxication induces the depletion of ATP thus leading to the depolarization of the cell membrane and release of glutamate. The depolarization and the excess amount of glutamate induce neuronal cell death in the center of the striatum.
2. The depolarization also induces the excess release of dopamine (DA) that leads to neuronal and astroglial cell death in the lateral striatum.
3. A very early state of neuronal damage was detected by argyrophil III silver impregnation.
4. Estrogen protected against while testosterone exacerbated the striatal lesions induced by 3-NPA.
5. Fetal striatal cells were transplanted into the injured striatum one month after 3-NPA intoxication. Once the cells survived, they extended neurites into the host striatum and resulted in the improvement of the motor symptom.
6. After 3-NPA application in vitro, astrocytes were more sensitive than neurons in the increase of [CaィイD1++ィエD1]ィイD2iィエD2, and they got into necrotic cell death.
7. bFGF, thrombin and melatonin protected in vitro astrocytic cell death induced by the application of 3-NPA, sodium nitroprusside (NO donor) or serum-free medium.