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Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [1];  [2];  [3]
  1. Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan (China)
  2. School of Medical Technology, Chung Shan Medical University, Taichung, Taiwan (China)
  3. Department of Physiology, Chung Shan Medical University, Taichung City 40201, Taiwan (China)

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.

OSTI ID:
20783457
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 212; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English

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