{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:57:00Z","timestamp":1788411420773,"version":"build-2803163510"},"reference-count":125,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prader\u2013Willi syndrome (PWS) is a rare, multisymptomatic genetic disorder caused by the absence or dysfunction of specific genes on chromosome 15. The genetic abnormality is anticipated to cause a dysfunction of the hypothalamus, which is also central in the regulation of the autonomic nervous system (ANS). Typical symptoms of PWS indicating a hypothalamic dysfunction include muscular hypotonia, poor growth, short stature, and feeding difficulties in infancy, which in early childhood are replaced by hyperphagia, leading to a high risk of obesity. Other characteristics, such as sleep difficulties, altered pain perception, delayed gastric emptying and constipation, blood pressure irregularities and dysregulated stress response, altered temperature regulation, delayed pupillary reaction, and urine retention and incontinence, all indicate a dysfunction of ANS. The ANS is usually divided into three parts: the sympathetic nervous system (SNS), which activates the fight-or-flight response during stress; the parasympathetic nervous system (PNS), which promotes calm and digestion; and the independent enteric nervous system (ENS), which regulates the gastrointestinal tract. Noradrenaline is the main neurotransmitter for the SNS, and acetylcholine for the PNS, while the ENS is regulated mainly by acetylcholine and serotonin. However, the ENS is modulated by both the SNS and the PNS, as well as many neuropeptides. Peptides regulating behavior, metabolism, appetite, and satiety have been extensively studied in PWS. However, studies of the role of neuropeptides in regulating other autonomic functions are limited and remain poorly understood. This review aims to synthesize current evidence from both animal models and human studies to explore potential mechanisms by which neuropeptides may contribute to autonomic dysfunction in individuals with PWS.<\/jats:p>","DOI":"10.3390\/ijms27010352","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:05:01Z","timestamp":1767193501000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuropeptides and the Autonomic Nervous System in Prader\u2013Willi Syndrome"],"prefix":"10.3390","volume":"27","author":[{"given":"Charlotte","family":"H\u00f6ybye","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-8593","authenticated-orcid":false,"given":"Maria","family":"Petersson","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1998). Prader\u2013Willi Syndrome, University of Washington."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S2213-8587(21)00002-4","article-title":"Endocrine disorders in Prader\u2013Willi syndrome: A model to understand and treat hypothalamic dysfunction","volume":"9","author":"Tauber","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13023-017-0673-6","article-title":"Early diagnosis and care is achieved but should be improved in infants with Prader\u2013Willi syndrome","volume":"12","author":"Bar","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1152\/physrev.1979.59.3.719","article-title":"Hypothalamic and genetic obesity in experimental animals: An autonomic and endocrine hypothesis","volume":"59","author":"Bray","year":"1979","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/oby.2003.6","article-title":"Autonomic nervous system activity and the state and development of obesity in Japanese school children","volume":"11","author":"Nagai","year":"2003","journal-title":"Obes. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0387-7604(00)00094-2","article-title":"Autonomic nervous system functions in obese children","volume":"22","author":"Yakinci","year":"2000","journal-title":"Brain Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10286-022-00909-7","article-title":"Autonomic nervous system dysfunction in Prader\u2013Willi syndrome","volume":"33","author":"Butler","year":"2023","journal-title":"Clin. Auton. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Janig, W. (1989). Autonomic Nervous System. Human Physiology, Springer. [2nd ed.].","DOI":"10.1007\/978-3-642-73831-9_16"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41583-025-00941-2","article-title":"Molecular and functional diversity of the autonomic nervous system","volume":"26","author":"Wang","year":"2025","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tach\u00e9, Y., Morley, J.E., and Brown, M.R. (1989). Neuropeptide Regulation of the Autonomic Nervous System. Neuropeptides and Stress, Springer. Hans Selye Symposia on Neuroendocrinology and Stress.","DOI":"10.1007\/978-1-4612-3514-9"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Caruso, A., Gaetano, A., and Scaccianoce, S. (2022). Corticotropin-releasing hormone: Biology and therapeutic opportunities. Biology, 11.","DOI":"10.3390\/biology11121785"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, H., Park, J., Liu, Y., Zhang, Y., Wang, Y., and Wang, Z. (2025). Oxytocin receptor expression and activation in parasympathetic brainstem cardiac vagal neurons. bioRxiv.","DOI":"10.1101\/2025.03.19.644204"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.psyneuen.2011.05.007","article-title":"Oxytocin specifically enhances valence-dependent parasympathetic responses","volume":"37","author":"Gamer","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.tins.2012.08.004","article-title":"Balance of brain oxytocin and vasopressin: Implications for anxiety, depression, and social behaviors","volume":"35","author":"Neumann","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Grinevich, V., and Oliveira, R. (2025). Thyrotropin-Releasing Hormone (TRH)-Containing Neuronal System in the Brain: Organization, Function and Evolution. Evolutionary and Comparative Neuroendocrinology, Springer. Masterclass in Neuroendocrinology.","DOI":"10.1007\/978-3-031-80209-6"},{"key":"ref_16","unstructured":"Paxinos, G. (2004). Central autonomic system. The Rat Nervous System, Academic Press. [3rd ed.]."},{"key":"ref_17","unstructured":"Ma, M.A., and Morrison, E.H. (2023). Neuroanatomy, Nucleus Suprachiasmatic. StatPearls, StatPearls Publishing."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0079-6123(08)62002-6","article-title":"Sympathoexcitatory neurons of the rostroventrolateral medulla and the origin of the sympathetic vasomotor tone","volume":"81","author":"Guyenet","year":"1989","journal-title":"Prog. Brain Res"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF02740606","article-title":"VIP: Molecular biology and neurobiological function","volume":"3","author":"Gozes","year":"1989","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1046\/j.1365-2265.2001.01392.x","article-title":"Ghrelin, not just another growth hormone secretagogue","volume":"55","author":"Toogood","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rehfeld, J.F. (2017). Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00047"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"H\u00f6ybye, C., and Petersson, M. (2025). The Role of the Arcuate Nucleus in Regulating Hunger and Satiety in Prader\u2013Willi Syndrome. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47030192"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12994","DOI":"10.1111\/jne.12994","article-title":"Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome","volume":"33","author":"Fliers","year":"2021","journal-title":"J. Neuroendocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0149-7634(05)80002-8","article-title":"Central functions of oxytocin","volume":"15","author":"Argiolas","year":"1991","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3109\/10799899109066412","article-title":"Appearance and Transient Expression of Vasopressin and Oxytocin Receptors in the Rat Brain","volume":"11","author":"Tribollet","year":"1991","journal-title":"J. Recept. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1677\/jme.0.0300109","article-title":"Molecular regulation of the oxytocin receptor in peripheral organs","volume":"30","author":"Kimura","year":"2003","journal-title":"J. Mol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1152\/physrev.2001.81.2.629","article-title":"The Oxytocin Receptor System: Structure, Function, and Regulation","volume":"81","author":"Gimpl","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.regpep.2003.12.017","article-title":"Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: A polymerase chain reaction study","volume":"119","author":"Monstein","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/cc2337","article-title":"Science review: Vasopressin and the cardiovascular system part 1--receptor physiology","volume":"7","author":"Holmes","year":"2003","journal-title":"Crit. Care"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Uvn\u00e4s-Moberg, K., Gross, M.M., Calleja-Agius, J., and Turner, J.D. (2024). The Yin and Yang of the oxytocin and stress systems: Opposites, yet interdependent and intertwined determinants of lifelong health trajectories. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1272270"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0079-6123(02)39024-1","article-title":"Cardiovascular effects of oxytocin","volume":"139","author":"Petersson","year":"2002","journal-title":"Prog. Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0304-3940(98)00729-0","article-title":"Oxytocin increases locus coeruleus alpha 2-adrenoreceptor responsiveness in rats","volume":"255","author":"Petersson","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.peptides.2011.03.007","article-title":"Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides","volume":"32","author":"Yang","year":"2011","journal-title":"Peptides"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1210\/en.2012-2206","article-title":"Oxytocin Receptor in the Hypothalamus Is Sufficient to Rescue Normal Thermoregulatory Function in Male Oxytocin Receptor Knockout Mice","volume":"154","author":"Kasahara","year":"2013","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vandendoren, M., Landen, J.G., Rogers, J.F., Killmer, S., Alimiri, B., Pohlman, C., Tattersall, G.J., Bedford, N.L., and Nelson, A.C. (2025). Oxytocin neurons signal state-dependent transitions from rest to thermogenesis and behavioral arousal in social and non-social settings. bioRxiv.","DOI":"10.7554\/eLife.108212.1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kummerfeld, D.F., Raabe, C.A., Brosius, J., Mo, D., Skryabin, B.V., and Rozhdestvensky, T.S. (2021). A comprehensive review of genetically engineered mouse models for Prader Willi Syndrome research. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073613"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Andrieu, D., Meziane, H., Marly, F., Angelats, C., Fernandez, P.A., and Muscatelli, F. (2006). Sensory defects in Necdin deficient mice result from a loss of sensory neurons correlated within an increase of developmental programmed cell death. BMC Dev. Biol., 6.","DOI":"10.1186\/1471-213X-6-56"},{"key":"ref_38","first-page":"573","article-title":"Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader\u2013Willi syndrome: A study of five cases","volume":"80","author":"Swaab","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1651-2227.1997.tb18369.x","article-title":"Prader\u2014Willi syndrome and the hypothalamus","volume":"86","author":"Swaab","year":"1997","journal-title":"Acta Paediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/ajmg.a.31606","article-title":"Whole genome microarray analysis of gene expression in Prader\u2013Willi syndrome","volume":"143","author":"Bittel","year":"2007","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/ajmg.a.37488","article-title":"Elevated plasma oxytocin levels in children with Prader\u2013Willi syndrome compared with healthy unrelated siblings","volume":"170","author":"Johnson","year":"2015","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S1096-6374(03)00077-7","article-title":"Peptides associated with hyperphagia in adults with Prader\u2013Willi syndrome before and during GH treatment","volume":"13","author":"Barkeling","year":"2003","journal-title":"Growth Horm. IGF Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S0006-3223(98)00190-5","article-title":"Cerebrospinal fluid levels of oxytocin in Prader\u2013Willi syndrome: A preliminary report","volume":"4","author":"Martin","year":"1998","journal-title":"Biol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sparapni, S. (2021). The biology of vasopressin. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010089"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e144450","DOI":"10.1172\/JCI144450","article-title":"Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model","volume":"131","author":"Borie","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rice, L.J., Agu, J., Carter, C.S., Harris, J.C., Nazarloo, H.P., Naanai, H., and Einfeld, S.L. (2023). The relationship between endogenous oxytocin and vasopressin levels and the Prader\u2013Willi syndrome behaviour phenotype. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1183525"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112429","DOI":"10.1016\/j.ijpsycho.2024.112429","article-title":"The relationship between cardiac activity, behaviour and endogenous oxytocin and vasopressin in Prader\u2013Willi Syndrome: An exploratory study","volume":"205","author":"Rice","year":"2024","journal-title":"Int. J. Psychophysiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1210\/jcem.83.2.4542","article-title":"Attenuation of the polypeptide 7B2, prohormone convertase PC2, and vasopressin in the hypothalamus of some Prader-Willi patients: Indications for a processing defect","volume":"83","author":"Swaab","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF01403704","article-title":"MR of the pituitary in patients with Prader\u2013Willi syndrome: Size determination and imaging findings","volume":"26","author":"Miller","year":"1996","journal-title":"Pediatr. Radiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"113674","DOI":"10.1016\/j.celrep.2024.113674","article-title":"Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice","volume":"43","author":"Kumari","year":"2024","journal-title":"Cell Rep."},{"key":"ref_51","first-page":"102972","article-title":"Neuropeptide Y and the autonomic nervous system","volume":"239","author":"Robertson","year":"2022","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1464-410X.2006.05938.x","article-title":"Distribution of neuropeptide Y-containing nerves in the neurogenic and non-neurogenic detrusor","volume":"97","author":"Haferkamp","year":"2006","journal-title":"BJU Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1210\/jcem.87.2.8230","article-title":"Hypothalamic NPY and agouti-related protein are increased in human illness but not in Prader\u2013Willi syndrome and other obese subjects","volume":"87","author":"Goldstone","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.freeradbiomed.2019.09.012","article-title":"Ghrelin effects on mitochondrial fitness modulates macrophage function","volume":"145","author":"Aguiar","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/157015909787602779","article-title":"Ghrelin in central neurons","volume":"7","author":"Ferrini","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/sj.ijo.0803001","article-title":"Ghrelin increases food intake in obese as well as lean subjects","volume":"29","author":"Druce","year":"2005","journal-title":"Int. J. Obes."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/nmo.12517","article-title":"A ghrelin receptor agonist is an effective colokinetic in rats with diet-induced constipation","volume":"27","author":"Pustovit","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5461","DOI":"10.1210\/jc.2002-020871","article-title":"High circulating ghrelin: A potential cause for hyperphagia and obesity in Prader\u2013Willi syndrome","volume":"87","author":"DelParigi","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1758-8111.2012.00032.x","article-title":"Autonomic nervous system dysfunction in obesity and Prader\u2013Willi syndrome: Current evidence and implications for future obesity therapies","volume":"1","author":"Haqq","year":"2011","journal-title":"Clin. Obes."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1210\/jc.2004-1651","article-title":"Hyperghrelinemia does not accelerate gastric emptying in Prader\u2013Willi syndrome patients","volume":"90","author":"Choe","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1093\/hmg\/ddw169","article-title":"Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits","volume":"25","author":"Maillard","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1152\/ajpgi.00434.2003","article-title":"Gastrointestinal satiety signals II. Cholecystokinin","volume":"286","author":"Moran","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/1096-8628(20001106)95:1<67::AID-AJMG13>3.0.CO;2-K","article-title":"Plasma cholecystokinin levels in Prader\u2013Willi syndrome and obese subjects","volume":"95","author":"Butler","year":"2000","journal-title":"Am. J. Med Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/00006676-198908000-00001","article-title":"Protein meal-stimulated pancreatic polypeptide secretion in Prader\u2013Willi syndrome of adults","volume":"4","author":"Tomita","year":"1989","journal-title":"Pancreas"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"436","DOI":"10.3346\/jkms.2007.22.3.436","article-title":"Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader\u2013Willi Syndrome","volume":"22","author":"Paik","year":"2007","journal-title":"J. Korean Med Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00726-006-0335-9","article-title":"The role of substance P in stress and anxiety responses","volume":"31","author":"Ebner","year":"2006","journal-title":"Amino Acids"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/1568026043451636","article-title":"Substance P: Structure, function, and therapeutics","volume":"4","author":"Datar","year":"2004","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_69","first-page":"685","article-title":"Mechanisms and controllers of eccrine sweating in humans","volume":"2","author":"Shibasaki","year":"2010","journal-title":"Front. Biosci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Butler, M.G., Nelson, T.A., Driscoll, D.J., and Manzardo, A.M. (2015). Evaluation of plasma substance p and beta-endorphin levels in children with Prader\u2013Willi syndrome. J. Rare Disord., 3.","DOI":"10.1002\/ajmg.a.37103"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","article-title":"The physiology of glucagon-like peptide 1","volume":"87","author":"Holst","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.peptides.2013.01.014","article-title":"Glucagon-like peptides 1 and 2 in health and disease: A review","volume":"44","author":"Marathe","year":"2013","journal-title":"Peptides"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1210\/en.2011-0174","article-title":"Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4","volume":"152","author":"Kanoski","year":"2011","journal-title":"Endocrinology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1229086","DOI":"10.1080\/23312025.2016.1229086","article-title":"The physiological role of the brain GLP-1 system in stress","volume":"2","author":"Holt","year":"2016","journal-title":"Congent. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.npep.2011.06.001","article-title":"In adults with Prader\u2013Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels","volume":"45","author":"Purtell","year":"2011","journal-title":"Neuropeptides"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"146","DOI":"10.4274\/jcrpe.galenos.2023.2023-7-7","article-title":"Serum Ghrelin and Glucagon-like Peptide 1 Levels in Children with Prader-Willi and Bardet-Biedl Syndromes","volume":"16","author":"Tekin","year":"2024","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bueno, M., Boixadera-Planas, E., Blanco-Hinojo, L., Esteba-Castillo, S., Gim\u00e9nez-Palop, O., Torrents-Rodas, D., Pujol, J., Corripio, R., Deus, J., and Caix\u00e0s, A. (2021). Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader\u2013Willi Syndrome?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215170"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/cen.14583","article-title":"The effects of glucagon-like peptide (GLP)-1 receptor agonists on weight and glycaemic control in Prader\u2013Willi syndrome: A systematic review","volume":"96","author":"Ng","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Mieda, M., Tsujino, N., and Sakurai, T. (2013). Differential roles of orexin receptors in the regulation of sleep\/wakefulness. Front. Endocrinol., 4.","DOI":"10.3389\/fendo.2013.00057"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41593-023-01365-w","article-title":"Control and coding of pupil size by hypothalamic orexin neurons","volume":"26","author":"Grujic","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"29480","DOI":"10.1038\/srep29480","article-title":"The integrative role of orexin\/hypocretin neurons in nociceptive perception and analgesic regulation","volume":"6","author":"Inutsuka","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Jaszberenyi, M., Thurzo, B., Bagaso, Z., Vecsei, L., and Tanake, M. (2024). The Orexin\/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress. Biomedicines, 12.","DOI":"10.3390\/biomedicines12020448"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1002\/ajmg.a.37777","article-title":"Higher plasma orexin a levels in children with Prader\u2013Willi syndrome compared with healthy unrelated sibling controls","volume":"170","author":"Manzardo","year":"2016","journal-title":"Am. J. Med Genet. A"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/ng2114","article-title":"The imprinted gene Magel2 regulates normal circadian output","volume":"39","author":"Kozlov","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s10571-020-01015-w","article-title":"Regulation of Opioid Receptors by Their Endogenous Opioid Peptides","volume":"41","author":"Gupta","year":"2021","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/S0196-9781(00)00345-4","article-title":"Endogenous opiates: 1999","volume":"21","author":"Vaccarino","year":"2000","journal-title":"Peptides"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Zhu, C., Wan, R., and Li, S. (2025). The Hypothalamic-Pituitary-Adrenal Axis and Its Regulation. The Peripheral Existence and Effects of Corticotropin-Releasing Factor Family, Springer.","DOI":"10.1007\/978-981-96-5322-5"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.autneu.2006.01.014","article-title":"Role of brainstem TRH\/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding","volume":"125","author":"Wang","year":"2006","journal-title":"Auton. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41522-024-00571-z","article-title":"Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway","volume":"10","author":"Zhang","year":"2024","journal-title":"Biofilms Microbiomes"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Grootjen, L.N., Kerkhof, G.F., Juriaans, A.F., Trueba-Timmermans, D.J., and Hokken-Koelega, A.C.S. (2023). Acute stress response of the HPA-axis in children with Prader\u2013Willi syndrome: New insights and consequences for clinical practice. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1146680"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1210\/en.2010-0709","article-title":"Impaired hypothalamic regulation of endocrine function and delayed counterregulatory response to hypoglycemia in Magel2-null mice","volume":"152","author":"Tennese","year":"2011","journal-title":"Endocrinology"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pellikaan, K., Snijders, F., Rosenberg, A.G., Davidse, K., van den Berg, S.A.A., Visser, W.E., van der Lely, A.J., and de Graaff, L.C.G. (2021). Thyroid function in adults with Prader\u2013Willi syndrome: A cohort study and literature review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173804"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1515\/jpem-2018-0388","article-title":"Thyroid function in patients with Prader\u2013Willi syndrome: An Italian multicenter study of 339 patients","volume":"32","author":"Iughetti","year":"2019","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1124\/pr.112.006536","article-title":"Physiology, signaling and pharmacology of galanin peptides and receptors: Three decades of emerging diversity","volume":"67","author":"Holmes","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"729","DOI":"10.33549\/physiolres.933576","article-title":"The Galanin and Galanin Receptor Subtypes, its Regulatory Role in the Biological and Pathological Functions","volume":"66","author":"Sipkova","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00726-011-1184-8","article-title":"Vasoactive intestinal peptide: A neuropeptide with pleiotropic immune functions","volume":"45","author":"Delgado","year":"2013","journal-title":"Amino Acids"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s12031-008-9090-6","article-title":"The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide in the neural pathways controlling the lower urinary tract","volume":"36","author":"Yoshiyama","year":"2008","journal-title":"J. Mol. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e138576","DOI":"10.1172\/jci.insight.138576","article-title":"Loss of MAGEL2 in Prader\u2013Willi syndrome leads to decreased secretory granule and neuropeptide production","volume":"5","author":"Chen","year":"2020","journal-title":"JCI Insight"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/313054a0","article-title":"Calcitonin gene-related peptide is a potent vasodilator","volume":"313","author":"Brain","year":"1985","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s10194-017-0741-2","article-title":"Calcitonin gene-related peptide and pain: A systematic review","volume":"18","author":"Schou","year":"2017","journal-title":"J. Headache Pain."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1210\/endrev\/bnae022","article-title":"Structure and function of somatostatin and its receptors in endocrinology","volume":"46","author":"Zhang","year":"2025","journal-title":"Endocr. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1210\/jc.2004-0835","article-title":"Somatostatin infusion lowers plasma ghrelin without reducing appetite in adults with Prader\u2013Willi syndrome","volume":"89","author":"Tan","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s003810050021","article-title":"Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept","volume":"16","author":"Ventureyra","year":"2000","journal-title":"Childs Nerv. Syst."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s10286-024-01065-w","article-title":"Vagus nerve stimulation (VNS): Recent advances and future directions","volume":"34","author":"Austelle","year":"2024","journal-title":"Clin. Auton. Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Trifilio, E., Shortell, D., Olshan, S., O\u2019Neal, A., Coyne, J., Lamb, D., Porges, E., and Williamson, J. (2023). Impact of transcutaneous vagus nerve stimulation on healthy cognitive and brain aging. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1184051"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/ajmg.b.32472","article-title":"Reduced Gamma-Aminobutyric Acid Is Associated with Emotional and Behavioral Problems in Prader\u2013Willi Syndrome","volume":"171","author":"Rice","year":"2016","journal-title":"Am. J. Med Genet. B Neuropsychiatr. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0920-1211(94)00083-9","article-title":"Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures","volume":"20","author":"Hamberger","year":"1995","journal-title":"Epilepsy Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00702-014-1299-7","article-title":"The effect of transcutaneous vagus nerve stimulation on cortical excitability","volume":"122","author":"Capone","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Manning, K.E., Beresford-Webb, J.A., Aman, L.C.S., Ring, H.A., Watson, P.C., Porges, S.W., Oliver, C., Jennings, S.R., and Holland, A.J. (2019). Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader\u2013Willi Syndrome indicated by results from a non-blind study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223750"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"104855","DOI":"10.1016\/j.ridd.2024.104855","article-title":"Effects of long-term transcutaneous auricular vagus nerve stimulation on circadian vagal activity in people with Prader\u2013Willi Syndrome: A case-series","volume":"154","author":"Schmausser","year":"2024","journal-title":"Res. Dev. Disabil."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1152\/jn.00571.2019","article-title":"Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala","volume":"123","author":"Crane","year":"2020","journal-title":"J. Neurophysiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/0006-8993(92)90431-8","article-title":"Morphological and electrophysiological evidence for postsynaptic localization of functional oxytocin receptors in the rat dorsal motor nucleus of the vagus nerve","volume":"575","author":"Raggenbass","year":"1992","journal-title":"Brain Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Chen, Z., and Liu, K. (2025). Mechanism and Applications of Vagus Nerve Stimulation. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020122"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"goaf009","DOI":"10.1093\/gastro\/goaf009","article-title":"Efficacy of vagus nerve stimulation in gastrointestinal disorders: A systematic review","volume":"13","author":"Veldman","year":"2025","journal-title":"Gastroenterol. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Petersson, M., Hulting, A., Andersson, R., and Uvn\u00e4s-Moberg, K. (1999). Long-term changes in gastrin, cholecystokinin and insulin in response to oxytocin treatment. Neuroendocrinology, 69, 202\u2013208.","DOI":"10.1159\/000054420"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/ajmg.a.31687","article-title":"Plasma obestatin and ghrelin levels in subjects with Prader\u2013Willi syndrome","volume":"143","author":"Butler","year":"2007","journal-title":"Am. J. Med Genet. A"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Casello, S.M., Flores, R.J., Yarur, H.E., Wang, H., Awanyai, M., Arenivar, M.A., Jaime-Lara, R.B., Bravo-Rivera, H., and Tejeda, H.A. (2022). Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders. Front. Neural Circuits, 16.","DOI":"10.3389\/fncir.2022.796443"},{"key":"ref_118","first-page":"246","article-title":"Distinct promoter regions of the oxytocin receptor gene are hypomethylated in Prader\u2013Willi syndrome and in Prader\u2013Willi syndrome associated psychosis","volume":"12","author":"Heseding","year":"2022","journal-title":"Psychiatry"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Fountain, M.D., and Schaaf, C.P. (2016). Prader\u2013Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene. Diseases, 4.","DOI":"10.3390\/diseases4010002"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1093\/hmg\/9.20.3101","article-title":"Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader\u2013Willi syndrome","volume":"9","author":"Muscatelli","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e185159","DOI":"10.1172\/jci.insight.185159","article-title":"Investigation of a mouse model of Prader\u2013Willi Syndrome with combined disruption of Necdin and Magel2","volume":"10","author":"Barelle","year":"2025","journal-title":"JCI Insight"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7582","DOI":"10.1038\/s41380-021-01227-6","article-title":"Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism","volume":"26","author":"Bertoni","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e20162976","DOI":"10.1542\/peds.2016-2976","article-title":"The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader\u2013Willi Syndrome","volume":"139","author":"Tauber","year":"2017","journal-title":"Pediatrics"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Richer, L.P., Tan, Q., Butler, M.G., Avedzi, H.M., DeLorey, D.S., Peng, Y., Tun, H.M., Sharma, A.M., Ainsley, S., and Orsso, C.E. (2023). Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader\u2013Willi Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098013"},{"key":"ref_125","unstructured":"Price, C., and LaMotte, J. (2020). The power of touch. A Multidisciplinary Approach to Embodiment, Routledge."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:07:38Z","timestamp":1767193658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010352"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010352","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]}}}