title: Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo.
abstract: Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or AktsiRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH.
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China; Shenzhen Key Laboratory for Anti-ageing and Regenerative Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, China.
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Yan
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Rifang
authors.initials: R
authors.lastname: Liao
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wan
authors.affiliation: School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: wenhuazheng@umac.mo.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007031:Hypothalamus / Q000166:cytology; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; C496874:neuropeptide W, rat; D003346:Corticotropin-Releasing Hormone; D020932:Nerve Growth Factor
keywords: HPA axis; Neuropeptide W; Neurotrophins; PI3K/Akt