Hsieh Yih-Shou, Yang Shun-Fa, Chiou Hui-Ling, Kuo Dong-Yih
Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
Toxicol Appl Pharmacol. 2006 Apr 15;212(2):99-109. doi: 10.1016/j.taap.2005.07.006. Epub 2005 Aug 9.
Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.
苯丙胺（AMPH）是一种厌食剂。AMPH厌食作用的潜在机制归因于其对下丘脑神经肽Y（NPY）的抑制作用，NPY是大脑中的一种食欲刺激剂。本研究旨在探讨AMPH厌食作用背后的分子机制。结果表明，AMPH处理可减少食物摄入量，这与NPY mRNA水平的变化相关，但可增加下丘脑c-fos、c-jun和超氧化物歧化酶（SOD）mRNA水平。为了确定c-fos或c-jun是否参与AMPH的厌食反应，在自由活动的大鼠每日接受AMPH处理前1小时，向其脑内注射反义寡核苷酸，结果表明，敲低c-fos或c-jun可阻断这种厌食反应并恢复NPY mRNA水平。此外，敲低c-fos或c-jun可部分阻断可能参与NPY基因表达调节的SOD mRNA水平。提示c-fos/c-jun信号通路可能通过调节NPY基因表达参与AMPH介导的摄食抑制的中枢调节。
