The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour

Abstract

Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via 5 receptor types, termed Y1, Y2, Y4, Y5 and y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve-derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, since immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved.There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease. KeywordsBrain; Immune system; Neuropeptide Y The neuropeptide Y family and its receptors (Y1, Y2, Y4, Y5)The principal members of the neuropeptide Y (NPY) family of biologically active peptides are NPY, peptide YY (PYY) and pancreatic polypeptide (PP). Like other biologically active peptides, the NPY-related peptides are synthesized as large protein precursors which are

Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome

“…Thus, CgA is considered to act as an anti-inflammatory. Interactions between the neuroendocrine peptides/amines of the gastrointestinal tract and the immune system have been suggested to play an important role in the inflammatory/infectious process in the gastrointestinal tract [51][52][53][54][55][56]. It is therefore likely that the increase in CgA density in Thai subjects is a response defense mechanism against inflammation/infection that developed because of the high exposure to infectious agents and the development of a broad immune tolerance.…”

Neuro-Immune Networks in Gastrointestinal Disorders

“…NPY is involved in gut secretion and motility [31]. Moreover, NPY serves as a paracrine and autocrine immune modulator [32]. Innate and adaptive immune cells are cell targets of NPY, where it regulates NO production, T cell differentiation, activity of natural killer cells, and antigen-presenting cells [1, 32-35].…”

“…Moreover, NPY serves as a paracrine and autocrine immune modulator [32]. Innate and adaptive immune cells are cell targets of NPY, where it regulates NO production, T cell differentiation, activity of natural killer cells, and antigen-presenting cells [1, 32-35]. Several subtypes of Y receptor are expressed in different immune cells and species; for instance, Y1, Y2, and Y5 expression was also demonstrated in murine macrophages and rat granulocytes [36, 37].…”

“…Several subtypes of Y receptor are expressed in different immune cells and species; for instance, Y1, Y2, and Y5 expression was also demonstrated in murine macrophages and rat granulocytes [36, 37]. Therefore, the anti- or pro-inflammatory effect of NPY is dependent on Y receptor subtypes and its specific expression in certain immune cell subtypes [32]. In the context of colitis, NPY antisense oligodeoxynucleotide attenuated DSS colitis in the rat [38] and the genetic deletion of NPY decreased the severity of DSS colitis in mice [39].…”

Neuropeptid Y és P anyag immunreaktív idegrostok és immunkompetens sejtek változása hepatitisben

“…Az NPY antiinfl ammatorikus hatású Y1 és Y2/Y5 receptorokon keresztül: csökkenti a granulocytaakkomodációt, fagocitózist, peroxidok termelését, növeli a nitrogén-monoxid-képződést [33]. A legutóbbi irodalmi adatok azt is alátámasztják, hogy az NPY nagyon fontos szerepet játszik a gyulladás okozta rossz közérzet és stressz kiküszöbölésében is [34]. Tehát az NPY egy új potenciális lehetőség lehet a citokinmediált autoimmun és gyulladásos betegségek terápiájában, így az autoimmun hepatitisben is.…”