Amphetamine-evoked changes of oxidative stress and neuropeptide Y gene expression in hypothalamus: regulation by the protein kinase C-delta signaling.
Amphetamine (AMPH), a psychostimulant, is an appetite suppressant and may be regarded as a neurotoxin. It was reported that superoxide dismutase (SOD) and neuropeptide Y (NPY) participated in AMPH-mediated behavior response. However, molecular mechanisms underlying this action are not well known. Using feeding behavior as an indicator, this study investigated if protein kinase C (PKC)-delta signaling was involved. Rats were given daily with AMPH for 4 days. Changes in hypothalamic NPY, PKCdelta and SOD mRNA contents were measured and compared. Results showed that the up-regulations of PKCdelta and SOD mRNA levels following AMPH treatment were concomitant with the down-regulation of NPY mRNA level and the decrease of feeding. To further determine if PKCdelta was involved, intracerebroventricular infusions of PKCdelta antisense oligonucleotide were performed at 1h before daily AMPH treatment in freely moving rats, and results showed that PKCdelta knock-down could block the anorectic response and restore partially both NPY and SOD mRNA levels in AMPH-treated rats. It is suggested that central PKCdelta signaling may play a functional role in the regulation of AMPH-mediated appetite suppression via a modification of hypothalamic NPY gene expression. Moreover, the increase of SOD during AMPH treatment may favor this modification.
Kuo
Dong-Yih
DY
Department of Physiology, Chung Shan Medical University, Taichung City 40201, Taiwan, ROC. dykuo@csmu.edu.tw
Yang
Shun-Fa
SF
Chu
Shu-Chen
SC
Chu
Shu-Chen
SC
Chen
Chin-Hsiu
CH
Hsieh
Yih-Shou
YS
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051745:Protein Kinase C-delta / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D009478:Neuropeptide Y; D012333:RNA, Messenger; D000661:Amphetamine; D013482:Superoxide Dismutase; D051745:Protein Kinase C-delta