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Interrupting activator protein‐1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine
Author(s) -
Hsieh YihShou,
Yang ShunFa,
Chu ShuChen,
Kuo DongYih
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04919.x
Subject(s) - neuropeptide y receptor , orexigenic , endocrinology , medicine , activator (genetics) , neuropeptide , hypothalamus , chemistry , gene expression , messenger rna , biology , receptor , gene , biochemistry
The mechanism for phenylpropanolamine (PPA)‐induced anorexia has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an orexigenic agent abundant in the brain. However, molecular mechanisms behind this effect are not well known. In this study, we investigated whether activator protein‐1 (AP‐1) signaling was involved. Rats were daily treated with PPA for 4 days. Changes in hypothalamic NPY, c‐ fos , c‐ jun , superoxide dismutase (SOD)‐1, and SOD‐2 mRNA contents were measured and compared. Results showed that c‐ fos and c‐ jun mRNA levels were increased following PPA treatment, which were relevant to a reduction in NPY mRNA level. To further determine if c‐ fos /c‐ jun genes were involved in PPA anorexia, infusions of antisense oligonucleotide into cerebroventricle were performed before daily PPA treatment in freely moving rats. Results showed that either c‐ fos or c‐ jun knock down could block PPA anorexia and restore NPY mRNA content to normal level. It is suggested that AP‐1 signaling may participate in the central regulation of PPA‐mediated appetite suppression via the modulation of NPY gene expression. Moreover, this modulation might be partly because of the neuroprotective effect of AP‐1 since SOD gene was activated during PPA treatment.