| Project/Area Number |
14104009
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
GOTO Katsutoshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Pharmacology, Professor, 大学院・人間総合科学研究科, 教授 (30012660)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Takeshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Pharmacology, Associate Professor, 大学院・人間総合科学研究科, 助教授 (60251055)
YAMANAKA Akihiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Pharmacology, Assistant Professor, 大学院・人間総合科学研究科, 講師 (60323292)
三輪 佳宏 筑波大学, 大学院・人間総合科学研究科, 講師 (70263845)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥102,700,000 (Direct Cost: ¥79,000,000、Indirect Cost: ¥23,700,000)
Fiscal Year 2005: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2004: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
Fiscal Year 2003: ¥33,540,000 (Direct Cost: ¥25,800,000、Indirect Cost: ¥7,740,000)
Fiscal Year 2002: ¥35,620,000 (Direct Cost: ¥27,400,000、Indirect Cost: ¥8,220,000)
|
|---|
| Keywords | Orexin / Sleep and wakefulness / Feeding behavior / Transgenic mice / Knockout mice / Slice patch clamp / Neuronal network / Behavioral analysis / カルシウム感受性タンパク質 / カルシウム / イメージング / コレシストキニン / 破傷風毒素 / GFP / 免疫染色 / 睡眠 / セロトニン / アセチルコリン / ナルコレプシー / パッチクランプ / 遺伝子改変マウス / 脳室内投与 / カタプレキシー / 抗体 |
|---|
| Research Abstract |
Orexin is a neuropeptide newly identified in 1998. Little had been known about the physiological role of orexin since this peptide was identified as a natural ligand for the orphan G protein coupled receptor by means of "Reverse Pharmacological Strategy". Intracerebroventricular injection of synthesis orexin peptide induced feeding behavior in animals, suggesting that this peptide is involved in the regulation of feeding behavior. Behavioral analysis of the prepro-orexin knockout mice and orexin 2 receptor knockout mice revealed that these mice showed a phenotype strikingly similar to human narcolepsy in the dark period. These results suggest that orexin plays an important role in the regulation of sleep/wakefulness as well as in feeding behavior. To reveal neuronal networks which are involved in the sleep/wakefulness regulation, the afferent to orexin neurons was studied by electrophysiological or histochemical analysis. It was difficult to identify orexin neurons in the living tissue since a small number of orexin neurons are diffusely distributed in the lateral hypothalamic area. To facilitate finding orexin neurons, we made several lines of transgenic mice in which orexin neurons specifically express enhanced green fluorescent protein (EGFP) or retrograde tracer (TTC). Electrophysiological analysis using orexin/EGFP transgenic mice revealed that orexin neurons are inhibited by serotonin and noradrenaline. Histochemical analysis using orexin/GFP::TTC transgenic mice revealed that orexin neurons receive dense innervations from the amygdala and cholinergic neurons in the basal forebrain. In this study, we revealed a neuronal network involved in sleep/wakefulness and feeding behavior.
|
