{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:07:58Z","timestamp":1790446078146,"version":"4.1.0"},"reference-count":97,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods & Clinical Development"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.omtm.2022.09.012","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T06:39:52Z","timestamp":1664260792000},"page":"131-148","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"special_numbering":"C","title":["Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome"],"prefix":"10.1016","volume":"27","author":[{"given":"Nicholas J.","family":"Queen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunchang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavya","family":"Appana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj","family":"Komatineni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Wevrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-4985","authenticated-orcid":false,"given":"Lei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2022.09.012_bib1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00335-013-9454-2","article-title":"Recommendations for the investigation of animal models of Prader-Willi syndrome","volume":"24","author":"Resnick","year":"2013","journal-title":"Mamm. Genome"},{"key":"10.1016\/j.omtm.2022.09.012_bib2","first-page":"473941","article-title":"Prader-Willi syndrome: clinical aspects","volume":"2012","author":"Elena","year":"2012","journal-title":"J.\u00a0Obes."},{"key":"10.1016\/j.omtm.2022.09.012_bib3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1046\/j.1365-2788.1998.4260455.x","article-title":"Prader-Willi syndrome and cycloid psychoses","volume":"42","author":"Verhoeven","year":"1998","journal-title":"J.\u00a0Intellect. Disabil. Res."},{"key":"10.1016\/j.omtm.2022.09.012_bib4","series-title":"Catatonia in Autism Spectrum Disorders","first-page":"119","article-title":"Prader\u2013willi syndrome: a typical psychoses and motor dysfunctions","author":"Verhoeven","year":"2006"},{"key":"10.1016\/j.omtm.2022.09.012_bib5","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1210\/jcem.87.4.8414","article-title":"Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study","volume":"87","author":"Carrel","year":"2002","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.omtm.2022.09.012_bib6","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1210\/edrv.22.6.0447","article-title":"Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH","volume":"22","author":"Burman","year":"2001","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.omtm.2022.09.012_bib7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2147\/TCRM.S70068","article-title":"Growth hormone therapy for Prader-willi syndrome: challenges and solutions","volume":"12","author":"Grugni","year":"2016","journal-title":"Ther. Clin. Risk Manag."},{"key":"10.1016\/j.omtm.2022.09.012_bib8","doi-asserted-by":"crossref","first-page":"E1072","DOI":"10.1210\/jc.2012-3888","article-title":"Growth hormone research society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome","volume":"98","author":"Deal","year":"2013","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.omtm.2022.09.012_bib9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/gim.0b013e31822bead0","article-title":"Prader-Willi syndrome","volume":"14","author":"Cassidy","year":"2012","journal-title":"Genet. Med."},{"key":"10.1016\/j.omtm.2022.09.012_bib10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jpeds.2016.05.018","article-title":"The high direct medical costs of Prader-Willi syndrome","volume":"175","author":"Shoffstall","year":"2016","journal-title":"J.\u00a0Pediatr."},{"key":"10.1016\/j.omtm.2022.09.012_bib11","doi-asserted-by":"crossref","first-page":"e0194655","DOI":"10.1371\/journal.pone.0194655","article-title":"High levels of caregiver burden in Prader-Willi syndrome","volume":"13","author":"Kayadjanian","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2022.09.012_bib12","doi-asserted-by":"crossref","first-page":"e0248739","DOI":"10.1371\/journal.pone.0248739","article-title":"Characteristics and relationship between hyperphagia, anxiety, behavioral challenges and caregiver burden in Prader-Willi syndrome","volume":"16","author":"Kayadjanian","year":"2021","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2022.09.012_bib13","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/ng.2776","article-title":"Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism","volume":"45","author":"Schaaf","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib14","doi-asserted-by":"crossref","first-page":"e1003207","DOI":"10.1371\/journal.pgen.1003207","article-title":"Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice","volume":"9","author":"Mercer","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib15","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1093\/hmg\/ddv159","article-title":"Progressive postnatal decline in leptin sensitivity of arcuate hypothalamic neurons in the Magel2-null mouse model of Prader-Willi syndrome","volume":"24","author":"Pravdivyi","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib16","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":"10.1016\/j.omtm.2022.09.012_bib17","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1093\/hmg\/ddy216","article-title":"Impaired melanocortin pathway function in Prader-Willi syndrome gene-Magel2 deficient mice","volume":"27","author":"Oncul","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib18","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nn1073","article-title":"Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor","volume":"6","author":"Xu","year":"2003","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2022.09.012_bib19","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1365-2826.2007.01610.x","article-title":"Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function","volume":"19","author":"Nicholson","year":"2007","journal-title":"J.\u00a0Neuroendocrinol."},{"key":"10.1016\/j.omtm.2022.09.012_bib20","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1016\/j.celrep.2018.03.018","article-title":"A transcriptomic signature of the hypothalamic response to fasting and BDNF deficiency in Prader-Willi syndrome","volume":"22","author":"Bochukova","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.omtm.2022.09.012_bib21","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1093\/emboj\/19.6.1290","article-title":"BDNF regulates eating behavior and locomotor activity in mice","volume":"19","author":"Kernie","year":"2000","journal-title":"EMBO J."},{"key":"10.1016\/j.omtm.2022.09.012_bib22","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1038\/npp.2010.114","article-title":"Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models","volume":"35","author":"Schmidt","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.omtm.2022.09.012_bib23","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jad.2013.08.001","article-title":"BDNF promoter methylation and suicidal behavior in depressive patients","volume":"151","author":"Kang","year":"2013","journal-title":"J.\u00a0Affect. Disord."},{"key":"10.1016\/j.omtm.2022.09.012_bib24","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s11011-009-9157-2","article-title":"Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats","volume":"24","author":"Marais","year":"2009","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.omtm.2022.09.012_bib25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1126\/science.1129663","article-title":"Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior","volume":"314","author":"Chen","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.omtm.2022.09.012_bib26","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1210\/jc.2010-0127","article-title":"Lower brain-derived neurotrophic factor in patients with Prader-Willi syndrome compared to obese and lean control subjects","volume":"95","author":"Han","year":"2010","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.omtm.2022.09.012_bib27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrd3366","article-title":"Potential therapeutic uses of BDNF in neurological and psychiatric disorders","volume":"10","author":"Nagahara","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.omtm.2022.09.012_bib28","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1097\/00001756-200104170-00040","article-title":"Analysis of effects and pharmacokinetics of subcutaneously administered BDNF","volume":"12","author":"Kishino","year":"2001","journal-title":"Neuroreport"},{"key":"10.1016\/j.omtm.2022.09.012_bib29","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/0169-328X(95)00250-V","article-title":"Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF","volume":"36","author":"Poduslo","year":"1996","journal-title":"Mol. Brain Res."},{"key":"10.1016\/j.omtm.2022.09.012_bib30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.omtm.2017.09.005","article-title":"Molecular therapy of melanocortin-4-receptor obesity by an autoregulatory BDNF vector. Molecular therapy","volume":"7","author":"Siu","year":"2017","journal-title":"Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2022.09.012_bib31","doi-asserted-by":"crossref","first-page":"e12846","DOI":"10.1111\/acel.12846","article-title":"Hypothalamic gene transfer of BDNF promotes healthy aging in mice","volume":"18","author":"McMurphy","year":"2019","journal-title":"Aging Cell"},{"key":"10.1016\/j.omtm.2022.09.012_bib32","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1038\/npp.2016.100","article-title":"ProBDNF signaling regulates depression-like behaviors in Rodents under Chronic stress","volume":"41","author":"Bai","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.omtm.2022.09.012_bib33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/gt.2015.113","article-title":"AAV1\/2-mediated BDNF gene therapy in a transgenic rat model of Huntington's disease","volume":"23","author":"Connor","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtm.2022.09.012_bib34","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nm.1933","article-title":"Molecular therapy of obesity and diabetes by a physiological autoregulatory approach","volume":"15","author":"Cao","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2022.09.012_bib35","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.05.029","article-title":"Environmental and genetic activation of a brain-adipocyte BDNF\/leptin axis causes cancer remission and inhibition","volume":"142","author":"Cao","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.09.012_bib36","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/mt.2014.45","article-title":"Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice","volume":"22","author":"Liu","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.09.012_bib37","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1038\/sj.ijo.0801913","article-title":"The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis","volume":"25","author":"Cone","year":"2001","journal-title":"Int. J. Obes."},{"key":"10.1016\/j.omtm.2022.09.012_bib38","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1093\/hmg\/ddm225","article-title":"Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome","volume":"16","author":"Bischof","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib39","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":"10.1016\/j.omtm.2022.09.012_bib40","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1210\/en.2005-0419","article-title":"Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex","volume":"146","author":"Bariohay","year":"2005","journal-title":"Endocrinology"},{"key":"10.1016\/j.omtm.2022.09.012_bib41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0014-4886(95)90045-4","article-title":"Characteristics of BDNF-induced weight loss","volume":"131","author":"Pelleymounter","year":"1995","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.omtm.2022.09.012_bib42","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nmeth.1806","article-title":"A guide to analysis of mouse energy metabolism","volume":"9","author":"Tsch\u00f6p","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.omtm.2022.09.012_bib43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2337\/db10-0909","article-title":"Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity Pathogenesis","volume":"60","author":"Kaiyala","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.omtm.2022.09.012_bib44","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1111\/bph.13540","article-title":"Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist","volume":"173","author":"Bischof","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.omtm.2022.09.012_bib45","series-title":"Mood and Anxiety Related Phenotypes in Mice","first-page":"1","article-title":"The open field test","author":"Gould","year":"2009"},{"key":"10.1016\/j.omtm.2022.09.012_bib46","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/ajmg.b.30934","article-title":"Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2","volume":"150B","author":"Mercer","year":"2009","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib47","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/gbb.12378","article-title":"Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty","volume":"16","author":"Fountain","year":"2017","journal-title":"Gene Brain Behav."},{"key":"10.1016\/j.omtm.2022.09.012_bib48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10339-011-0430-z","article-title":"The novel object recognition memory: neurobiology, test procedure, and its modifications","volume":"13","author":"Antunes","year":"2012","journal-title":"Cognit. Process."},{"key":"10.1016\/j.omtm.2022.09.012_bib49","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1038\/nprot.2013.155","article-title":"Object recognition test in mice","volume":"8","author":"Leger","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.omtm.2022.09.012_bib50","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00213-009-1466-y","article-title":"Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety","volume":"204","author":"Thomas","year":"2009","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.omtm.2022.09.012_bib51","first-page":"50978","article-title":"Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice","author":"Angoa-Perez","year":"2013","journal-title":"J.\u00a0Vis. Exp."},{"key":"10.1016\/j.omtm.2022.09.012_bib52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biopsych.2014.11.010","article-title":"An early postnatal oxytocin treatment prevents social and learning deficits in adult mice deficient for Magel2, a gene involved in Prader-Willi syndrome and autism","volume":"78","author":"Meziane","year":"2015","journal-title":"Biol. Psychiatr."},{"key":"10.1016\/j.omtm.2022.09.012_bib53","doi-asserted-by":"crossref","DOI":"10.3791\/2473","article-title":"Assessment of social interaction behaviors","author":"Kaidanovich-Beilin","year":"2011","journal-title":"J.\u00a0Vis. Exp."},{"key":"10.1016\/j.omtm.2022.09.012_bib54","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The tail suspension test: a new method for screening antidepressants in mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.omtm.2022.09.012_bib55","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nrrheum.2016.209","article-title":"Leptin in the interplay of inflammation, metabolism and immune system disorders","volume":"13","author":"Abella","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.omtm.2022.09.012_bib56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.molmet.2013.04.001","article-title":"Adiponectin, driver or passenger on the road to insulin sensitivity?","volume":"2","author":"Ye","year":"2013","journal-title":"Mol. Metabol."},{"key":"10.1016\/j.omtm.2022.09.012_bib57","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/21623945.2017.1402151","article-title":"Adiponectin-leptin ratio: a promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk","volume":"7","author":"Fr\u00fchbeck","year":"2018","journal-title":"Adipocyte"},{"key":"10.1016\/j.omtm.2022.09.012_bib58","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCRESAHA.120.314458","article-title":"Adiponectin, leptin and cardiovascular disorders","volume":"128","author":"Zhao","year":"2021","journal-title":"Circ. Res."},{"key":"10.1016\/j.omtm.2022.09.012_bib59","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1073\/pnas.1114122109","article-title":"BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus","volume":"109","author":"Jeanneteau","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2022.09.012_bib60","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbi.2018.09.028","article-title":"Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice","volume":"75","author":"Xiao","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.omtm.2022.09.012_bib61","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1158\/2326-6066.CIR-15-0297","article-title":"Environmental and genetic activation of hypothalamic BDNF modulates T-cell immunity to exert an anticancer phenotype","volume":"4","author":"Xiao","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"10.1016\/j.omtm.2022.09.012_bib62","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":"10.1016\/j.omtm.2022.09.012_bib63","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cmet.2011.06.020","article-title":"White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis","volume":"14","author":"Cao","year":"2011","journal-title":"Cell Metabol."},{"key":"10.1016\/j.omtm.2022.09.012_bib64","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1210\/en.2015-1627","article-title":"Role of hypothalamic VGF in energy balance and metabolic adaption to environmental enrichment in mice","volume":"2016","author":"Foglesong","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.omtm.2022.09.012_bib65","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.omtm.2019.03.001","article-title":"Preclinical testing in translational animal models of Prader-Willi syndrome: overview and gap analysis","volume":"13","author":"Carias","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2022.09.012_bib66","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s11689-021-09373-2","article-title":"Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS clinical trial Consortium","volume":"13","author":"Schwartz","year":"2021","journal-title":"J.\u00a0Neurodev. Disord."},{"key":"10.1016\/j.omtm.2022.09.012_bib67","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.soard.2016.04.023","article-title":"Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse","volume":"12","author":"Arble","year":"2016","journal-title":"Surg. Obes. Relat. Dis."},{"key":"10.1016\/j.omtm.2022.09.012_bib68","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/01.mpg.0000304458.30294.31","article-title":"Critical analysis of bariatric procedures in Prader-Willi syndrome","volume":"46","author":"Scheimann","year":"2008","journal-title":"J.\u00a0Pediatr. Gastroenterol. Nutr."},{"key":"10.1016\/j.omtm.2022.09.012_bib69","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s40618-021-01574-9","article-title":"Obesity in Prader\u2013Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches","volume":"44","author":"Muscogiuri","year":"2021","journal-title":"J.\u00a0Endocrinol. Invest."},{"key":"10.1016\/j.omtm.2022.09.012_bib70","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.neubiorev.2012.05.005","article-title":"The effect of growth hormone treatment or physical training on motor performance in Prader\u2013Willi syndrome: a systematic review","volume":"36","author":"Reus","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.omtm.2022.09.012_bib71","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/cen.13953","article-title":"Physical exercise and Prader-Willi syndrome: a systematic review","volume":"90","author":"Morales","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.omtm.2022.09.012_bib72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/0145445507308582","article-title":"A mindfulness-based health wellness program for an adolescent with Prader-Willi syndrome","volume":"32","author":"Singh","year":"2008","journal-title":"Behav. Modif."},{"key":"10.1016\/j.omtm.2022.09.012_bib73","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/jgm.885","article-title":"Immune responses to AAV in a phase I study for Canavan disease","volume":"8","author":"McPhee","year":"2006","journal-title":"J.\u00a0Gene Med."},{"key":"10.1016\/j.omtm.2022.09.012_bib74","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1089\/hum.2008.022","article-title":"Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA","volume":"19","author":"Worgall","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2022.09.012_bib75","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S1474-4422(08)70065-6","article-title":"Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2\u2013neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial","volume":"7","author":"Marks","year":"2008","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.omtm.2022.09.012_bib76","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1016\/S0140-6736(07)60982-9","article-title":"Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial","volume":"369","author":"Kaplitt","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.omtm.2022.09.012_bib77","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.ymthe.2019.11.012","article-title":"A safe and reliable technique for CNS delivery of AAV vectors in the cisterna magna","volume":"28","author":"Taghian","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.09.012_bib78","doi-asserted-by":"crossref","first-page":"E225","DOI":"10.1210\/jc.2010-1733","article-title":"The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index","volume":"96","author":"Haqq","year":"2011","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.omtm.2022.09.012_bib79","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.yfrne.2013.01.002","article-title":"Mouse models of Prader-Willi Syndrome: a systematic review","volume":"34","author":"Bervini","year":"2013","journal-title":"Front. Neuroendocrinol."},{"key":"10.1016\/j.omtm.2022.09.012_bib80","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/gim.2016.53","article-title":"The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families","volume":"19","author":"Fountain","year":"2017","journal-title":"Genet. Med."},{"key":"10.1016\/j.omtm.2022.09.012_bib81","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1002\/ajmg.a.40650","article-title":"Schaaf-Yang syndrome overview: Report of 78 individuals","volume":"176","author":"McCarthy","year":"2018","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib82","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3390\/diseases4010002","article-title":"Prader-Willi syndrome and Schaaf-Yang syndrome: neurodevelopmental diseases intersecting at the MAGEL2 gene","volume":"4","author":"Fountain","year":"2016","journal-title":"Diseases"},{"key":"10.1016\/j.omtm.2022.09.012_bib83","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1523\/JNEUROSCI.22-07-02650.2002","article-title":"Estrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus","volume":"22","author":"Solum","year":"2002","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.omtm.2022.09.012_bib84","doi-asserted-by":"crossref","first-page":"11110","DOI":"10.1073\/pnas.92.24.11110","article-title":"Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor","volume":"92","author":"Sohrabji","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2022.09.012_bib85","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neuroscience.2013.01.025","article-title":"Steroid hormones and BDNF","volume":"239","author":"Pluchino","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.omtm.2022.09.012_bib86","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1093\/hmg\/ddx311","article-title":"The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways","volume":"26","author":"Wijesuriya","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.09.012_bib87","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.cmet.2019.08.005","article-title":"Partial leptin reduction as an insulin sensitization and weight loss strategy","volume":"30","author":"Zhao","year":"2019","journal-title":"Cell Metabol."},{"key":"10.1016\/j.omtm.2022.09.012_bib88","first-page":"e3769","article-title":"The tail suspension test","author":"Can","year":"2012","journal-title":"JoVE"},{"key":"10.1016\/j.omtm.2022.09.012_bib89","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/2041-210X.12584","article-title":"BORIS: a free, versatile open-source event-logging software for video\/audio coding and live observations","volume":"7","author":"Friard","year":"2016","journal-title":"Methods Ecol. Evol."},{"key":"10.1016\/j.omtm.2022.09.012_bib90","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3164\/jcbn.09-83","article-title":"A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-Alcoholic fatty Pancreas disease (NAFPD) in C57BL\/6 mice fed a high fat diet","volume":"46","author":"Fraulob","year":"2010","journal-title":"J.\u00a0Clin. Biochem. Nutr."},{"key":"10.1016\/j.omtm.2022.09.012_bib91","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods (San Diego, Calif.)"},{"key":"10.1016\/j.omtm.2022.09.012_bib92","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.09.008","article-title":"Adipose PTEN regulates adult adipose tissue homeostasis and redistribution via a PTEN-leptin-sympathetic loop","volume":"30","author":"Huang","year":"2019","journal-title":"Mol. Metabol."},{"key":"10.1016\/j.omtm.2022.09.012_bib93","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1186\/s12859-017-1934-z","article-title":"ImageJ2: ImageJ for the next generation of scientific image data","volume":"18","author":"Rueden","year":"2017","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.omtm.2022.09.012_bib94","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.omtm.2022.09.012_bib95","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1194\/jlr.D023788","article-title":"Adiposoft: automated software for the analysis of white adipose tissue cellularity in histological sections","volume":"53","author":"Galarraga","year":"2012","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.omtm.2022.09.012_bib96","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1109\/TSMC.1979.4310076","article-title":"A threshold selection method from gray-level histograms","volume":"9","author":"Otsu","year":"1979","journal-title":"IEEE Trans. Syst. Man Cybern."},{"key":"10.1016\/j.omtm.2022.09.012_bib97","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1093\/bioinformatics\/btw413","article-title":"MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ","volume":"32","author":"Legland","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Molecular Therapy - Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050122001371?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050122001371?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:28:10Z","timestamp":1762421290000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050122001371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":97,"alternative-id":["S2329050122001371"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2022.09.012","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2022.09.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors.","name":"copyright","label":"Copyright"}]}}