C-terminal peptide of preproorexin enhances brain-derived neurotrophic factor expression in rat cerebrocortical cells and recognition memory in mice

Hiroshi Tsuneki*, Kosuke Honda, Yurika Sekine, Koji Yahata, Moeka Yasue, Masashi Fujishima, Ryuta Takeda, Tsutomu Wada, Toshiyasu Sasaoka*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

1 被引用数 (Scopus)

抄録

During the production of orexin A and B from preproorexin, a common precursor protein, in hypothalamic orexin neurons, C-terminal peptide (herein called preproorexin C-peptide) is concomitantly produced via post-translational processing. The predicted three-dimensional structure of preproorexin C-peptide is similar among mammalian species, suggestive of a conserved function in the mammalian brain. However, C-peptide has long been regarded as a non-functional peptide. We herein examined the effects of rat and/or mouse preproorexin C-peptide on gene expression and cell viability in cultured rat cerebrocortical cells and on memory behavior in C57BL/6J mice. Rat and mouse C-peptides both increased brain-derived neurotrophic factor (Bdnf) mRNA levels. Moreover, C-peptide enhanced high K+-, glutamate-, and BDNF-induced increases in Bdnf mRNA levels without affecting forskolin-induced Bdnf expression. H-89, a protein kinase A inhibitor, blocked C-peptide-induced Bdnf expression, whereas rolipram, a phosphodiesterase inhibitor, enhanced this effect. Intracellular cyclic AMP concentrations were elevated by C-peptide. These results demonstrate that preproorexin C-peptide promoted Bdnf mRNA expression by a cyclic AMP-dependent mechanism. Eleven amino acids at the N terminus of rat preproorexin C-peptide exerted similar effects on Bdnf expression as full-length preproorexin C-peptide. Preproorexin C-peptide also exerted protective effects against CoCl2-induced neuronal cell death. An intracerebroventricular injection of mouse preproorexin C-peptide induced c-fos and Bdnf expression in the cerebral cortex and hippocampus and enhanced novel object recognition memory in mice. Collectively, the present results show that preproorexin C-peptide is a functional substance, at least in some pharmacological and neuronal settings.

本文言語英語
論文番号176306
ジャーナルEuropean Journal of Pharmacology
964
DOI
出版ステータス出版済み - 2024/02/05

ASJC Scopus 主題領域

  • 薬理学

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