{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:41:22Z","timestamp":1793727682638,"version":"4.6.1"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL174521-01A1"],"award-info":[{"award-number":["1R01HL174521-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1R01HL174521-01A1"],"award-info":[{"award-number":["1R01HL174521-01A1"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM149404"],"award-info":[{"award-number":["P30GM149404"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P30GM149404"],"award-info":[{"award-number":["P30GM149404"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fulbright Foreign Student Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic d-galactose (d-gal) treatment is a model to induce accelerated aging-like phenotypes in rodents. However, the sex differences in behavioral and musculoskeletal manifestations of this model are not well understood. Heme oxygenase-1 (HO-1) is a cytoprotective protein that may have anti-aging properties. The goal of this study was to better understand the sex differences in the behavioral and musculoskeletal effects of chronic d-gal treatment in C57BL\/6J mice, as well as the role of HO-1 induction or inhibition. Eight-week-old male and female mice received daily saline or d-gal injections (500 mg\/kg, s.c.) for 12 weeks. After this time, mice in the d-gal group were randomized into three groups (n = 6\/group\/sex): d-gal, d-gal + cobalt protoporphyrin (CoPP) (5 mg\/kg, s.c. weekly), and d-gal + zinc deutroporphyrin bisglycol (ZnBG) (42 mg\/kg, i.p. triweekly) for a period of 4 weeks. Open-field, novel-object recognition, Barnes maze, grip strength, micro-computed tomography (\u00b5-CT), histology, and protein analysis were performed. Chronic d-gal treatment resulted in a sexual dimorphic response, with female mice being more prone to develop deficits in both short- and long-term spatial memory as well as in non-spatial memory. Male mice exhibited deficits only in long-term spatial memory when treated chronically with d-gal. Inhibition of HO-1 was protective in both females and males. Chronic d-gal treatment did not accelerate the development of osteoporosis or sarcopenia in either males or females. Our results demonstrate a sexual dimorphic response to the chronic effects of d-gal treatment on aging, with greater effects in females than in males, which is dependent on HO-1.<\/jats:p>","DOI":"10.3390\/biom16040548","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:49:44Z","timestamp":1775641784000},"page":"548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Behavior and Musculoskeletal Effects of Chronic D-Galactose Treatment in Mice: Role of Heme Oxygenase-1"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3514-5992","authenticated-orcid":false,"given":"Sally","family":"Wahba","sequence":"first","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minya 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-2170","authenticated-orcid":false,"given":"Olufunto O.","family":"Badmus","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Wasson","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-9752","authenticated-orcid":false,"given":"Elshymaa A.","family":"Abdel-Hakeem","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minya 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merhan Mamdouh","family":"Ragy","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minya 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa Mohamad","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minya 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-6824","authenticated-orcid":false,"given":"Daniela","family":"R\u00fcedi-Bettschen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-4008","authenticated-orcid":false,"given":"David E.","family":"Stec","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20428","DOI":"10.18632\/oncotarget.14670","article-title":"Skeletal muscle aging: Influence of oxidative stress and physical exercise","volume":"8","author":"Gomes","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","unstructured":"World Health Organization (2026, February 17). 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