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.脑内潜伏-TGF-β的激活机制据报道，基质金属蛋白酶(MMP)参与失活的潜伏-TGF-β的激活，因此在引起疲劳的运动中，脑内MMP的活性增加。运动后脑桥、延髓、中脑、间脑等部位MMP-9的表达变化。 2．大鼠脑内TGF-β。通过原位杂交和免疫组化染色，发现TGF-β 1型和2型受体在脑下丘脑室旁核（PVH）中表达。3．TGF-β作用机制的神经化学研究。 -β在脑中的作用通过脑池内施用TGF-β对大鼠脑的一些区域进行神经递质细胞外浓度的测量，观察到以下变化：细胞外浓度增加。下丘脑腹内侧核（VMH）血清素和去甲肾上腺素减少，下丘脑外侧区（LHA）和内侧前额皮质（mPFC）血清素减少，未发现细胞外多巴胺浓度发生变化。4．脑池内施用的 TGF-β 对周围组织的影响激素浓度的变化（肾上腺素、去甲肾上腺素、通过脑池内施用 TGF-b，测量血清中这些激素的浓度没有变化。然而，这种治疗导致后腿骨骼肌中脂蛋白脂肪酶 (LPL) 的活性增加。此外，肝脏和腓肠肌红色部分中脂肪代谢的关键物质丙二酰辅酶A的浓度降低。