Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity
Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity
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DOI：
10.1016/j.physbeh.2010.06.006
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发表时间：
2010-10-05
影响因子：
2.9
通讯作者：
Inoue, Kazuo
中科院分区：
文献类型：
--
作者：
Fujikawa, Teppei;Fujita, Ryo;Inoue, Kazuo
我们以前曾报道，转化生长因子（TGF）-β在脑脊液（CSF）中参与的机制，由中枢神经系统运动后自发运动活动（SMA）的调节。然而，目前还不清楚是什么生理条件触发了TGF-β的激活。我们假设，在运动的早期阶段观察到的脂肪酸（FA）氧化产生的能量不足激活了CSF中的TGF-β。为了验证这一假设，我们研究了FA氧化抑制剂巯基乙酸（MA）是否能诱导CSF中TGF-β的活化和SMA的减少。腹膜内（i. p.）给予MA激活了大鼠CSF中的TGF-β，并抑制了SMA;另一方面，2-脱氧葡萄糖（一种碳水化合物氧化抑制剂）抑制了SMA，但未能激活CSF中的TGF-β。脑池内注射抗TGF-β抗体可消除MA对SMA的抑制作用。我们还发现，通过迷走神经切断术消除了通过腹膜内MA给药对CSF中SMA的抑制和TGF-β的激活。我们的数据表明，CSF中的TGF-β通过迷走神经抑制FA氧化而激活，随后诱导SMA抑制。(C)2010年爱思唯尔公司All rights reserved.
We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA. (C) 2010 Elsevier Inc. All rights reserved.