User:Cbarry773/sandbox
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the mammalian central nervous system, comprised of the brain and spinal cord. It secreted alongside other neurotransmitters such as GABA and glutamate. [1][2][3]
Function
[edit]Neuropeptide Y has been identified as being synthesized in GABAnergic inhibitory neurons and acts as a neurotransmitter during cellular communication. Neuropeptide Y is majorly expressed in interneurons.[4] NPY exerts most of its effects through G-protein coupled receptor proteins, mainly Y1, Y2, Y4, and Y6.[2](tat). All receptors have been indicated as participants in post-synaptic transmission activity, but the Y2 receptor has also been found to be involved in pre-synaptic processing.[1]
High concentrations of Neuropeptide Y synthesis and action have been found in the hypothalamus and hippocampus, specifically in the arcuate nucleus (ARC) and dentate gyrus. The arcuate nucleus has been found to have one of the highest concentrations of NPY. This allows NPY to regulate neuroendocrine release of various hypothalamic hormones such as luteinizing hormone. [5] Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus along with a variety of other brain areas. [6]
Cell Growth
[edit]Neuropeptide Y has been indicated as playing an important role in cell neurogenesis in various parts of the brain. Two particular brains areas of where NPY effect neurogenesis are the sub-ventricular zone and the dentate gyrus of the hippocampus. These areas are where cell growth and proliferation occur into adulthood.[7]
Dentate Gyrus
[edit]The dentate gyrus is significantly involved in cell proliferation, a process modulated by various internal factors including Neuropeptide Y. Reduction or elimination of NPY released by interneurons decreased cell growth in this brain area. NPY affects neurogenesis by interacting with ERK kinase signaling pathways.[8]Additionally, NPY acting on and stimulating Y1 receptors present on progenitor cell membranes in order to increase cell proliferation. [7]
Sub-ventricular zone
[edit]Similar to the dentate gyrus, NPY has been found to increase cellular proliferation and differentiation in the sub-ventricular zone by specifically activating Y1 receptors in the ERK1/2 pathway. Additionally, NPY was found in neuronal fibers that pass through the sub-ventricular zone and extend to other brain areas. A variety of other effects and physiological processes involving NPY in the sub-ventricular zone have been discovered, many of which involve neuron migration patterns.[9]
It was found that after blocking NPY expression in mouse olfactory epithelium, the amount of olfactory precursor cells decreased by half. This in turn caused the mice to develop an lower amount of olfactory cells overall. This study exemplified NPY's influence on precursor cells. [10]
Connection to disorders
[edit]Alcoholism
[edit]The role of Neuropeptide Y has gained substantial attention for it's involvement with alcoholism due to its the diverse range of physiological effects. NPY neurons have been shown to interact with dopaminergic reward and emotion pathways in the nucleus accumbens and amygdala, respectively. NPY expression levels and alcohol preference have been shown exhibit an inverse relationship. Expression levels are dependent on the brain area of interest. This indicates that baseline NPY levels could possibly influence innate alcohol preferences. [2]
Previous studies have identified NPY's anxiolytic effects to a possible therapeutic drug target for alcoholism.[11] As stated before, NPY levels and ethanol intake show an inverse relationship, therefore, therefore, increasing NPY availability could decrease alcohol intake. By creating a chemical antagonist for a Y2 receptor that would indirectly act as an agonist and stimulate Y1 receptors, alcohol consumption was successfully decreased in rats. [12] Additionally, another similar study identified that NPY expression may be connected to behavioral regulation in relation to alcohol dependence. Administration of neuropeptide Y was found to reduce binge-drinking behavior. [13] Although, it has been shown that NPY gene expression, mRNA or neuropeptide levels are not influenced by long-term alcohol consumption, but changes do occur during withdrawal from alcohol. These findings show that Neuropeptide Y has varying effects on alcohol consumption. [12]
Stress and Anxiety
[edit]Neuropeptide Y is considered to be a anxiolytic endogenous peptide and its levels can be modulated by stress. NPY has connections to the HPA axis and is believed to be necessary for stress modulation. [14] It has been shown that higher levels of the Y1 and Y5 receptors in the amygdala result in reduced level of anxiety.[15] Additionally, the Y1 receptor has been linked to anxiolytic effects in the forebrain while Y2 has been associated with the pons.[4]
References
[edit]- ^ a b Decressac, M.; Barker, R.A. "Neuropeptide Y and its role in CNS disease and repair". Experimental Neurology. 238 (2): 265–272. doi:10.1016/j.expneurol.2012.09.004.
- ^ a b c Robinson, Stacey L.; Thiele, Todd E. The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. pp. 177–197. doi:10.1016/bs.irn.2017.06.005.
- ^ Heilig, M.; Widerlöv, E. (1995). "Neurobiology and clinical aspects of neuropeptide Y". Critical Reviews in Neurobiology. 9 (2–3): 115–136. ISSN 0892-0915. PMID 8581979.
- ^ a b Kask, Ants; Harro, Jaanus; Hörsten, Stephan von; Redrobe, John P.; Dumont, Yvan; Quirion, Rémi. "The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y". Neuroscience & Biobehavioral Reviews. 26 (3): 259–283. doi:10.1016/s0149-7634(01)00066-5.
- ^ Acuna-Goycolea, Claudio; Tamamaki, Nobuaki; Yanagawa, Yuchio; Obata, Kunihiko; van den Pol, Anthony N. (2005-08-10). "Mechanisms of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Inhibition of Identified Green Fluorescent Protein-Expressing GABA Neurons in the Hypothalamic Neuroendocrine Arcuate Nucleus". Journal of Neuroscience. 25 (32): 7406–7419. doi:10.1523/jneurosci.1008-05.2005.
- ^ Kautz, Marin; Charney, Dennis S.; Murrough, James W. "Neuropeptide Y, resilience, and PTSD therapeutics". Neuroscience Letters. 649: 164–169. doi:10.1016/j.neulet.2016.11.061.
- ^ a b Decressac, Mickael; Wright, Ben; David, Belin; Tyers, Pam; Jaber, Mohamed; Barker, Roger A.; Gaillard, Afsaneh (2011-03-01). "Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis". Hippocampus. 21 (3): 233–238. doi:10.1002/hipo.20765. ISSN 1098-1063.
- ^ Howell, Owain W.; Doyle, Kharen; Goodman, Jeffrey H.; Scharfman, Helen E.; Herzog, Herbert; Pringle, Ashley; Beck-Sickinger, Annette G.; Gray, William P. (2005-05-01). "Neuropeptide Y stimulates neuronal precursor proliferation in the post-natal and adult dentate gyrus". Journal of Neurochemistry. 93 (3): 560–570. doi:10.1111/j.1471-4159.2005.03057.x. ISSN 1471-4159.
{{cite journal}}: no-break space character in|title=at position 13 (help) - ^ Malva, J.O.; Xapelli, S.; Baptista, S.; Valero, J.; Agasse, F.; Ferreira, R.; Silva, A.P. "Multifaces of neuropeptide Y in the brain – Neuroprotection, neurogenesis and neuroinflammation". Neuropeptides. 46 (6): 299–308. doi:10.1016/j.npep.2012.09.001.
- ^ Hansel, D. E.; Eipper, B. A.; Ronnett, G. V. (2001-04-19). "Neuropeptide Y functions as a neuroproliferative factor". Nature. 410 (6831): 940–944. doi:10.1038/35073601. ISSN 1476-4687.
- ^ Thorsell, Annika; Mathé, Aleksander A. (2017). "Neuropeptide Y in Alcohol Addiction and Affective Disorders". Frontiers in Endocrinology. 8. doi:10.3389/fendo.2017.00178. ISSN 1664-2392.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Ciccocioppo, Roberto; Gehlert, Donald R.; Ryabinin, Andrey; Kaur, Simranjit; Cippitelli, Andrea; Thorsell, Annika; Lê, Anh D.; Hipskind, Philip A.; Hamdouchi, Chafiq. "Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond". Alcohol. 43 (7): 491–498. doi:10.1016/j.alcohol.2009.08.003.
- ^ Sparrow, Angela M; Lowery-Gionta, Emily G; Pleil, Kristen E; Li, Chia; Sprow, Gretchen M; Cox, Benjamin R; Rinker, Jennifer A; Jijon, Ana M; Peňa, José (2012/05). "Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors". Neuropsychopharmacology. 37 (6): 1409–1421. doi:10.1038/npp.2011.327. ISSN 1740-634X.
{{cite journal}}: Check date values in:|date=(help) - ^ Reichmann, Florian; Holzer, Peter. "Neuropeptide Y: A stressful review". Neuropeptides. 55: 99–109. doi:10.1016/j.npep.2015.09.008.
- ^ Dumont, Yvan; Quirion, Rémi. "Neuropeptide Y Pathways in Anxiety-Related Disorders". Biological Psychiatry. 76 (11): 834–835. doi:10.1016/j.biopsych.2014.09.015.