{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:17:12Z","timestamp":1790821032193,"version":"4.1.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100001316","name":"Abbott Laboratories","doi-asserted-by":"publisher","award":["ZA69"],"award-info":[{"award-number":["ZA69"]}],"id":[{"id":"10.13039\/100001316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Physiology & Behavior"],"published-print":{"date-parts":[[2017,3]]},"DOI":"10.1016\/j.physbeh.2016.12.025","type":"journal-article","created":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T10:30:44Z","timestamp":1482834644000},"page":"93-99","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats"],"prefix":"10.1016","volume":"170","author":[{"given":"Daniel G.","family":"Kougias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-584X","authenticated-orcid":false,"given":"Emily R.","family":"Hankosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-8791","authenticated-orcid":false,"given":"Joshua M.","family":"Gulley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Juraska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1\u20132","key":"10.1016\/j.physbeh.2016.12.025_bb0005","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0531-5565(02)00160-2","article-title":"The neurobiology of memory changes in normal aging","volume":"38","author":"Erickson","year":"2003","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev.psych.48.1.339","article-title":"The use of animal models to study the effects of aging on cognition","volume":"48","author":"Gallagher","year":"1997","journal-title":"Annu. Rev. Psychol."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0015","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bmb\/ldp033","article-title":"Age-associated cognitive decline","volume":"92","author":"Deary","year":"2009","journal-title":"Br. Med. Bull."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0020","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1196\/annals.1396.028","article-title":"Dietary influences on cognitive function with aging: from high-fat diets to healthful eating","volume":"1114","author":"Parrott","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"4","key":"10.1016\/j.physbeh.2016.12.025_bb0025","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1212\/WNL.0b013e3182436598","article-title":"Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging","volume":"78","author":"Bowman","year":"2012","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.physbeh.2016.12.025_bb0030","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/jpn.12234","article-title":"Dietary supplementation of \u03b2-hydroxy-\u03b2-methylbutyrate in animals - a review","volume":"99","author":"Szcze\u015bniak","year":"2015","journal-title":"J. Anim. Physiol. Anim. Nutr. (Berlin)"},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0035","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tins.2009.11.003","article-title":"mTOR signaling: at the crossroads of plasticity, memory and disease","volume":"33","author":"Hoeffer","year":"2010","journal-title":"Trends Neurosci."},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0040","doi-asserted-by":"crossref","first-page":"B106","DOI":"10.1093\/gerona\/55.2.B106","article-title":"Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory","volume":"55","author":"Thornton","year":"2000","journal-title":"J. Gerontol."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0045","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bbr.2014.02.005","article-title":"mTOR and autophagy in normal brain aging and caloric restriction ameliorating age-related cognition deficits","volume":"264","author":"Yang","year":"2014","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0050","article-title":"Effects of a hydroxy-methyl butyrate (HMB) on cognitive flexibility and working memory in an animal model of aging","author":"Hankosky","year":"2016","journal-title":"Nutr. Neurosci."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0055","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.neurobiolaging.2016.01.004","article-title":"Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates aging effects in the dendritic tree of pyramidal neurons in the medial prefrontal cortex of both male and females rats","volume":"40","author":"Kougias","year":"2016","journal-title":"Neurobiol. Aging"},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0060","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrn1809","article-title":"Neural plasticity in the ageing brain","volume":"7","author":"Burke","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0065","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0197-4580(84)90084-8","article-title":"Spatial learning and motor deficits in aged rats","volume":"5","author":"Gage","year":"1984","journal-title":"Neurobiol. Aging"},{"issue":"4","key":"10.1016\/j.physbeh.2016.12.025_bb0070","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1037\/bne0000080","article-title":"Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze","volume":"129","author":"Gallagher","year":"1993","journal-title":"Behav. Neurosci."},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0075","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2008.11.004","article-title":"Aging of the human ovary and testis","volume":"299","author":"Perheentupa","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0080","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1210\/endo-103-5-1855","article-title":"Patterns of sex steroid and gonadotropin secretion in aging female rats","volume":"103","author":"Huang","year":"1978","journal-title":"Endocrinology"},{"key":"10.1016\/j.physbeh.2016.12.025_bb0085","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000122968","article-title":"Effect of ovariectomy on plasma LH, FSH, estradiol, and progesterone and medial basal hypothalamic LHRH concentrations in old and young rats","volume":"30","author":"Wise","year":"1980","journal-title":"Neuroendocrinology"},{"key":"10.1016\/j.physbeh.2016.12.025_bb0090","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0197-4580(02)00004-0","article-title":"Aging and sex influence the anatomy of the rat anterior cingulate cortex","volume":"23","author":"Markham","year":"2002","journal-title":"Neurobiol. Aging"},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0095","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0301-0082(00)00025-3","article-title":"Neuroprotection by estradiol","volume":"63","author":"Garcia-Segura","year":"2001","journal-title":"Prog. Neurobiol."},{"issue":"7","key":"10.1016\/j.physbeh.2016.12.025_bb0100","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1097\/gme.0b013e31824d1fc4","article-title":"Effects of long-term treatment with estrogen and medroxyprogesterone acetate on synapse number in the medial prefrontal cortex of aged female rats","volume":"19","author":"Chisholm","year":"2012","journal-title":"Menopause"},{"issue":"10","key":"10.1016\/j.physbeh.2016.12.025_bb0105","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1210\/en.2012-1412","article-title":"The effects of long-term treatment with estradiol and medroxyprogesterone acetate on tyrosine hydroxylase fibers and neuron number in the medial prefrontal cortex of aged female rats","volume":"153","author":"Chisholm","year":"2012","journal-title":"Endocrinology"},{"issue":"3","key":"10.1016\/j.physbeh.2016.12.025_bb0110","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1006\/nlme.1999.3948","article-title":"Sex differences and estropausal phase effects on water maze performance in aged rats","volume":"74","author":"Warren","year":"2000","journal-title":"Neurobiol. Learn. Mem."},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0115","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.yhbeh.2010.03.018","article-title":"Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats","volume":"58","author":"Lowry","year":"2010","journal-title":"Horm. Behav."},{"issue":"6","key":"10.1016\/j.physbeh.2016.12.025_bb0120","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1037\/0735-7044.110.6.1309","article-title":"Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training","volume":"110","author":"Perrot-Sinal","year":"1996","journal-title":"Behav. Neurosci."},{"issue":"9","key":"10.1016\/j.physbeh.2016.12.025_bb0125","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1017\/S0007114515003050","article-title":"Comparison of availability and plasma clearance rates of \u03b2-hydroxy-\u03b2-methylbutyrate delivery in the free acid and calcium salt forms","volume":"114","author":"Fuller","year":"2015","journal-title":"Br. J. Nutr."},{"issue":"11","key":"10.1016\/j.physbeh.2016.12.025_bb0130","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0955-2863(01)00182-6","article-title":"Beta-hydroxy-beta-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans","volume":"12","author":"Vukovich","year":"2001","journal-title":"J. Nutr. Biochem."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0135","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1550-2783-9-18","article-title":"Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats","volume":"9","author":"Wilson","year":"2012","journal-title":"J. Int. Soc. Sports Nutr."},{"issue":"3","key":"10.1016\/j.physbeh.2016.12.025_bb0140","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0197-4580(89)90062-6","article-title":"Temporally graded, age-related impairments in spatial memory in the rat","volume":"10","author":"Aitken","year":"1989","journal-title":"Neurobiol. Aging"},{"issue":"12","key":"10.1016\/j.physbeh.2016.12.025_bb0145","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1007\/s00216-014-7694-y","article-title":"Quantitative determination of \u03b2-hydroxymethylbutyrate and leucine in culture media and microdialysates from ratbrain by UHPLC-tandem mass spectrometry","volume":"406","author":"Santos-Fandila","year":"2014","journal-title":"Anal. Bioanal. Chem."},{"issue":"17","key":"10.1016\/j.physbeh.2016.12.025_bb0150","doi-asserted-by":"crossref","first-page":"6587","DOI":"10.1523\/JNEUROSCI.20-17-06587.2000","article-title":"Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats","volume":"20","author":"Smith","year":"2000","journal-title":"J. Neurosci."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0155","first-page":"68","article-title":"HMB use and its relationship to exercise-induced muscle damage and performance during exercise","volume":"2","author":"Routhier","year":"2007","journal-title":"Int. Sport Med. J."},{"issue":"11","key":"10.1016\/j.physbeh.2016.12.025_bb0160","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s11745-013-3836-9","article-title":"Aging induces tissue-specific changes in cholesterol metabolism in rat brain and liver","volume":"48","author":"Smiljanic","year":"2013","journal-title":"Lipids"},{"issue":"7","key":"10.1016\/j.physbeh.2016.12.025_bb0165","doi-asserted-by":"crossref","first-page":"902","DOI":"10.15252\/emmm.201303711","article-title":"Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents","volume":"6","author":"Martin","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.physbeh.2016.12.025_bb0170","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1152\/ajpendo.00314.2007","article-title":"Signaling pathways initiated by \u03b2-hydroxy-\u03b2-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli","author":"Eley","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0175","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S1744-1161(11)70054-0","article-title":"OP054 regulation of neuronal survival factors by \u03b2-hydroxy-\u03b2-methylbutyrate (HMB): future therapeutic implications","volume":"6","author":"Lopez-Pedrosa","year":"2011","journal-title":"Clin. Nutr. Suppl."},{"issue":"31","key":"10.1016\/j.physbeh.2016.12.025_bb0180","doi-asserted-by":"crossref","first-page":"8048","DOI":"10.1523\/JNEUROSCI.0671-06.2006","article-title":"Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-mammalian target of rapamycin pathway","volume":"26","author":"Dash","year":"2006","journal-title":"J. Neurosci."},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0185","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ghir.2010.12.006","article-title":"Chronic supplementation of beta-hydroxy-beta methylbutyrate (HM\u03b2) increases the activity of the GH\/IGF-I axis and induces hyperinsulinemia in rats","volume":"21","author":"Gerlinger-Romero","year":"2011","journal-title":"Growth Hormon. IGF Res."},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0190","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.arr.2005.02.001","article-title":"Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging","volume":"4","author":"Sonntag","year":"2005","journal-title":"Ageing Res. Rev."},{"issue":"1\u20133","key":"10.1016\/j.physbeh.2016.12.025_bb0195","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejphar.2004.02.047","article-title":"Insulin-like growth factor-I, cognition and brain aging","volume":"490","author":"van Dam","year":"2004","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.physbeh.2016.12.025_bb0200","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.neuroscience.2004.08.001","article-title":"Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning","volume":"129","author":"Ramsey","year":"2004","journal-title":"Neuroscience"},{"issue":"3","key":"10.1016\/j.physbeh.2016.12.025_bb0205","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0306-4522(98)00143-2","article-title":"Insulin-like growth factor-1 ameliorates age-related behavioral deficits","volume":"87","author":"Markowska","year":"1998","journal-title":"Neuroscience"},{"issue":"5","key":"10.1016\/j.physbeh.2016.12.025_bb0210","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00213-013-3310-7","article-title":"Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats","volume":"231","author":"Nelson","year":"2014","journal-title":"Psychopharmacology"},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0215","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1210\/en.2012-1698","article-title":"Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I","volume":"154","author":"Witty","year":"2013","journal-title":"Endocrinology"},{"issue":"4","key":"10.1016\/j.physbeh.2016.12.025_bb0220","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.yfrne.2006.09.001","article-title":"Cross-talk between estrogen receptors and insulin-like growth factor-I receptor in the brain: cellular and molecular mechanisms","volume":"27","author":"Mendez","year":"2006","journal-title":"Front. Neuroendocrinol."},{"issue":"Suppl. 1","key":"10.1016\/j.physbeh.2016.12.025_bb0225","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1016\/j.psyneuen.2007.03.001","article-title":"Estradiol, insulin-like growth factor-I and brain aging","volume":"32","author":"Garcia-Segura","year":"2007","journal-title":"Psychoneuroendocrinology"},{"issue":"3","key":"10.1016\/j.physbeh.2016.12.025_bb0230","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1006\/hbeh.2002.1819","article-title":"Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the morris water maze","volume":"42","author":"Markham","year":"2002","journal-title":"Horm. Behav."},{"issue":"2","key":"10.1016\/j.physbeh.2016.12.025_bb0235","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1037\/h0033536","article-title":"Species-specific behavior and acquisition of avoidance behavior in rats","volume":"81","author":"Grossen","year":"1972","journal-title":"J. Comp. Physiol. Psychol."},{"issue":"4","key":"10.1016\/j.physbeh.2016.12.025_bb0240","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/0091-3057(88)90413-3","article-title":"Thigmotaxis as a test for anxiolytic activity in rats","volume":"31","author":"Treit","year":"1988","journal-title":"Pharmacol. Biochem. Behav."}],"container-title":["Physiology & Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031938416307843?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031938416307843?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T11:53:00Z","timestamp":1617623580000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0031938416307843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":48,"alternative-id":["S0031938416307843"],"URL":"https:\/\/doi.org\/10.1016\/j.physbeh.2016.12.025","relation":{},"ISSN":["0031-9384"],"issn-type":[{"value":"0031-9384","type":"print"}],"subject":[],"published":{"date-parts":[[2017,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats","name":"articletitle","label":"Article Title"},{"value":"Physiology & Behavior","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.physbeh.2016.12.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}