FoxO3a suppresses neuropeptide W expression in neuronal cells and in rat hypothalamus and its implication in hypothalamic-pituitary-adrenal (HPA) axis

Abstract

FoxO3a, a forkhead family member of transcription factors, is involved in the regulation of cell metabolism, proliferation, differentiation and apoptosis. However, whether FoxO3a participates in the regulation of glucocorticoids induced-hypothalamic-pituitary-adrenal (HPA) dysfunction is still unknown. Our present results indicate that dexamethasone(DEX) increased FoxO3a expression in PC12 and hypothalamic neuronal cultures in correlation to reduced expression of NPW, a process that could be blocked by GR2 antagonist. DEX restrained the phosphorylation of Akt and FoxO3a, but not ERK1/2 phosphorylation, resulting with FoxO3a nuclear localization. Overexpression of FoxO3a inhibited NPW expression, while FoxO3a knockdown by siRNA had the opposite effect. The regulatory region of NPW promoter contains multiple FoxO3a binding sites, and FoxO3a bonding to these sites inhibited its transcriptional activity. In a rat model, chronic administration of corticosterone reduced animals' body weight and sucrose consumption and caused stress-depression like behavior. Corticosterone treatment induced a marked increase in FoxO3a levels, while decreased the expression of NPW protein in the hypothalamus. Immunofluorescent double labeling demonstrated that FoxO3a and NPW were collocated in the hypothalamus. Taken together, these data indicate that NPW is a new direct downstream target gene of FoxO3a. FoxO3a suppressed the transcription of NPW and modulated glucocorticoids-induced HPA dysfunction by directly regulating the expression of NPW. Thus, present findings suggest that FoxO3a and NPW may be potential therapeutic targets for endocrine and psychiatric disorders.

Effect of The Critical Period and Gene Silencing on Blood Cellular Traits in Local Chicken and Level of Welfare

“…The reason for the superiority of T6 is attributed to siRNA technology, which reduced heat stress by controlling corticosterone secretion from the adrenal cortex. Therefore, siRNA performs its function through full conjugation according to the Watson-Crick rule with mRNA, Thus, the decomposition of mRNA occurs, and the cell cannot recognize it, and this prevents gene expression in RNA molecules, due to the destruction of the messenger RNA, and this will lead to a decrease in the level of corticosterone [21]. As for the reason for the decrease in lymphocytes in the control treatment, it is due to stress, which weakens the immunity, as it was proven that the high temperature leads to the secretion of corticosterone, and that hormone works to decompose and destroy lymphoid tissue and change the ratio of both L / H [22].…”

Neuropeptide W Exhibits Preventive and Therapeutic Effects on Acetic Acid-Induced Colitis Via the Modulation of Cyclooxygenase Enzyme System

“…The novel peptide neuropeptide W (NPW), occurring with 23 (NPW23) or 30 (NPW30) amino acid residues, binds to its orphan G-protein-coupled GPR7 (NPBWR1) and GPR8 (NPBWR2) receptors [15,16]. In parallel with its abundant expression in the central nervous system and the gastrointestinal tract, NPW was originally shown to function in the control of feeding behavior and energy homeostasis [16][17][18][19]. NPW increases arterial myogenic tone, heart rate, blood pressure, and plasma levels of epinephrine and norepinephrine in rats, exhibiting its modulatory role in the local and central control of cardiovascular function and sympathetic nervous outflow [20][21][22].…”