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Function of cytokine in the brain in manifestation of central fatigue and its involvement to the regulation of metabolism

脑细胞因子在中枢性疲劳表现中的作用及其参与代谢调节

基本信息

批准号：
16580097
负责人：
INOUE Kazuo
金额：
$ 2.5万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

1. Activation mechanism of latant-TGF-β in the brainBecause matrix metalloproteinases (MMP) are reported to be involved to activation of inacvtive latent-TGF-β, the activity of MMP in the brain were determined in the exercise which caused fatigue. Increases in the expression of MMP-9 were found after exercise in pons, medulla oblongata, mesencephalon, and diencephalon.2. Expression sites of receptors for TGF-β in the rat brain.Type 1 and type 2 receptor for TGF-β were found to be expressed in paraventricular nucleus of hypothalamus (PVH) in the brain by in situ hybridization and immunohistochemical staining.3. Neurochemical studies of mechanism of TGF-β action in the brainMeasurements of the extracellular concentration of neurotransmitters with intracisternal administration of TGF-β were conducted in some regions of rat brain. Following changes were observed : increases in the extracellular concentrations of serotonin and noradrenaline in the ventromedial nucleus of hypothalamus (VMH), decreases in those of serotonin in lateral hypothalamic area (LHA) and medial prefrontal cortex (mPFC). No changes in the extracellular concentration of dopamine was found.4. Mechanism of action of intracisternally administered TGF-β on peripheral tissuesChanges in concentrations of hormones (adrenalin, noradrenaline, insulin, glucagon, and leptin) in serum were measured. No changes was found in these hormones concentrations by intracisternal administration of TGF-b. However, this treatment caused increase in the activity of lipoprotein lipase (LPL) in skeletal muscles of hind legs. In addition, the concentrations of malonyl-CoA which is a key substance of fat metabolism decreased in the liver and red part of gastrocnemius muscle.

1.潜伏性TGF-β在脑内的激活机制由于基质金属蛋白酶（matrix metalloproteinases，MMP）参与了无活性的潜伏性TGF-β的激活，因此我们在运动性疲劳中测定了脑内MMP的活性。运动后，MMP-9在脑桥、延髓、中脑和间脑的表达增加. TGF-β受体在大鼠脑内的表达部位：原位杂交和免疫组化染色发现TGF-β 1型和2型受体在下丘脑室旁核（PVH）表达. TGF-β在脑内作用机制的神经化学研究用脑池内注射TGF-β的方法，测定了大鼠脑内某些区域细胞外神经递质的浓度。下丘脑腹内侧核（VMH）细胞外5-羟色胺和去甲肾上腺素浓度升高，下丘脑外侧区（LHA）和内侧前额叶皮质（mPFC）细胞外5-羟色胺和去甲肾上腺素浓度降低。细胞外多巴胺浓度无明显变化.脑池内注射TGF-β对外周组织的作用机制测定血清中激素（肾上腺素、去甲肾上腺素、胰岛素、胰高血糖素和瘦素）浓度的变化。脑池内注射TGF-β后，这些激素的浓度没有变化。然而，该处理引起后腿骨骼肌中脂蛋白脂酶（LPL）活性的增加。此外，脂肪代谢的关键物质丙二酰辅酶A在肝脏和腓肠肌红部的浓度降低。