Hsieh Yih-Shou, Chen Pei-Ni, Yu Ching-Han, Chen Chia-Hui, Tsai Tsung-Ta, Kuo Dong-Yih
Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
Neurotoxicology. 2015 May;48:131-41. doi: 10.1016/j.neuro.2015.03.011. Epub 2015 Mar 28.
Amphetamine (AMPH) treatment can suppress appetite and increase oxidative stress in the brain. AMPH-induced appetite suppression is associated with the regulation of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. The present study explored whether antioxidants, including glutathione S-transferase (GST) and glutathione peroxidase (GP), were involved in this NPY/CART-mediated appetite control. Rats were treated daily with AMPH for four days. Changes in food intake and expression levels of hypothalamic NPY, CART, GST, and GP were examined and compared. Results showed that, in AMPH-treated rats, (1) food intake and NPY expression decreased, while CART, GST, and GP expression increased; (2) NPY knockdown in the brain enhanced the decrease in NPY and the increases in CART, GST, and GP expression; and (3) central inhibition of reactive oxygen species production decreased GST and GP and modulated AMPH anorexia and the expression levels of NPY and CART. The present results suggest that oxidative stress in the brain participates in regulating NPY/CART-mediated appetite control in AMPH-treated rats. These results may advance the knowledge regarding the molecular mechanism of AMPH-evoked or NPY/CART-mediated appetite suppression.
苯丙胺（AMPH）治疗可抑制食欲并增加大脑中的氧化应激。AMPH诱导的食欲抑制与下丘脑神经肽Y（NPY）和可卡因及苯丙胺调节转录物（CART）的调节有关。本研究探讨了包括谷胱甘肽S-转移酶（GST）和谷胱甘肽过氧化物酶（GP）在内的抗氧化剂是否参与这种由NPY/CART介导的食欲控制。大鼠每天接受AMPH治疗四天。检测并比较食物摄入量以及下丘脑NPY、CART、GST和GP的表达水平变化。结果表明，在接受AMPH治疗的大鼠中，（1）食物摄入量和NPY表达下降，而CART、GST和GP表达增加；（2）大脑中NPY基因敲低增强了NPY的下降以及CART、GST和GP表达的增加；（3）中枢抑制活性氧生成降低了GST和GP，并调节了AMPH引起的厌食以及NPY和CART的表达水平。目前的结果表明，大脑中的氧化应激参与调节AMPH治疗大鼠中由NPY/CART介导的食欲控制。这些结果可能会推进有关AMPH诱发或NPY/CART介导的食欲抑制分子机制的知识。
