Neuropeptide Y (29-64), amide, human, a 36-aa peptide, binds to five G-protein-coupled receptors (Y1, Y2, Y4, Y5, and y6). Widely distributed in the central and peripheral nervous systems as well as in other peripheral tissues, Neuropeptide Y plays pivotal roles in regulating appetite, blood pressure, cardiac contractility, intestinal secretion, and stem-cell biology[1-2]. Neuropeptide Y modulates cellular functions of NK-cells, and circulating levels of Neuropeptide Y are correlated with NK activity[3].
In vitro, neurons were pretreated with Neuropeptide Y (0.5, 1, and 2μM) for 24h and then exposed to Aβ’s pathogenic fragment 25-35 (Aβ25-35) (50μM) for 48h. At 24 and 48h, 2μM Neuropeptide Y completely abolished Aβ25-35 induced toxicity, and comparable neuroprotective effects on neuronal survival were seen with 1μM and 0.5μM pretreatments[4]. After 24h of treatment with Neuropeptide Y (0, 20, or 200nM), bone-marrow-derived macrophages (BMMs) exhibited a significant up-regulation of matrix metalloproteinases (MMPs)-3 mRNA expression and protein secretion[5].
In vivo, following intracerebral administration of Neuropeptide Y (0, 24, 78, 156, or 235pmol in 5μl), rats receiving injections into the perifornical hypothalamus (PFH) consumed significantly more food than those injected into the nucleus accumbens (NAC), and a clear dose-dependent effect was also observed[6]. Central administration of Neuropeptide Y (4.5nmol) to male Sprague-Dawley rats significantly elevated NAC dopamine (DA) release to 150% of baseline and produced a step-wise increase in NAC norepinephrine efflux[7].
References:
[1] Peng S, Zhou YL, Song ZY, Lin S. Effects of Neuropeptide Y on Stem Cells and Their Potential Applications in Disease Therapy. Stem Cells Int. 2017;2017:6823917.
[2] Li C, Wu X, Liu S, Zhao Y, Zhu J, Liu K. Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases. Front Neurosci. 2019;13:869.
[3] Bedoui S, Lechner S, Gebhardt T, et al. NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization. J Neuroimmunol. 2002;132(1-2):25-33.
[4] Croce N, Ciotti MT, Gelfo F, et al. Neuropeptide Y protects rat cortical neurons against β-amyloid toxicity and re-establishes synthesis and release of nerve growth factor. ACS Chem Neurosci. 2012;3(4):312-318.
[5] Choi B, Shin MK, Kim EY, et al. Elevated Neuropeptide Y in Endothelial Dysfunction Promotes Macrophage Infiltration and Smooth Muscle Foam Cell Formation. Front Immunol. 2019;10:1701.
[6] Brown CM, Coscina DV, Fletcher PJ. The rewarding properties of neuropeptide Y in perifornical hypothalamus vs. nucleus accumbens. Peptides. 2000;21(8):1279-1287.
[7] Quarta D, Leslie CP, Carletti R, Valerio E, Caberlotto L. Central administration of NPY or an NPY-Y5 selective agonist increase in vivo extracellular monoamine levels in mesocorticolimbic projecting areas. Neuropharmacology. 2011;60(2-3):328-335.
Neuropeptide Y (29-64), amide, human，一种由36个氨基酸组成的肽，可与五种G蛋白偶联受体（Y1、Y2、Y4、Y5和y6）结合。Neuropeptide Y广泛分布于中枢与外周神经系统及其他外周组织，Neuropeptide Y在调控食欲、血压、心肌收缩力、肠道分泌和干细胞生物学中发挥关键作用[1-2]。Neuropeptide Y还能调节NK细胞的细胞功能，且循环Neuropeptide Y水平与NK活性呈正相关[3]。
在体外，神经元先用Neuropeptide Y（0.5、1、2μM）预处理24h，再用Aβ的致病片段25-35（Aβ25-35，50μM）处理48h。在24和48h时，2μM Neuropeptide Y完全抵消了Aβ25-35诱导的毒性，1μM和0.5μM预处理亦产生类似的神经保护作用[4]。骨髓来源巨噬细胞（BMMs）经Neuropeptide Y（0、20或200nM）处理24h后，基质金属蛋白酶-3（MMP-3）的mRNA表达及蛋白分泌显著上调[5]。
在体内，经脑内给予Neuropeptide Y（0、24、78、156或235pmol，5μl）后，注射至下丘脑摄食区（PFH）的大鼠摄食量显著高于注射至伏隔核（NAC）的大鼠，且呈现明显的剂量依赖性[6]。向雄性Sprague-Dawley大鼠中枢注射Neuropeptide Y（4.5nmol）可将伏隔核多巴胺（DA）释放量提升至基线的150%，并使伏隔核去甲肾上腺素（NE）外排呈阶梯式增加[7]。