{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:30:33Z","timestamp":1789047033566,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018726","name":"Torbat Heydariyeh University of Medical Sciences","doi-asserted-by":"publisher","award":["404000061"],"award-info":[{"award-number":["404000061"]}],"id":[{"id":"10.13039\/100018726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, leading to severe motor impairments.\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      negatively regulates neuronal survival, while\n                      <jats:italic>Sirtuin\u20101 (Sirt1)<\/jats:italic>\n                      supports mitochondrial function and oxidative stress resistance. Given the neuroprotective properties of Vitamin D3 (VitD3) and resveratrol, this study examined whether their combined administration could modulate\n                      <jats:italic>Sirt1<\/jats:italic>\n                      and\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      expression and attenuate neurodegeneration in a 6\u2010hydroxydopamine (6\u2010OHDA) model of PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male Swiss mice were assigned to six groups: Control, Sham, 6\u2010OHDA, 6\u2010OHDA + Resveratrol (5\u00a0mg\/kg), 6\u2010OHDA + VitD3 (0.1\u00a0\u00b5g\/kg), and 6\u2010OHDA + Res + VitD3. Behavioral performance was evaluated using open field, footprint, wire grip, and rotarod tests. Neuronal integrity within the ventral tegmental area (VTA) was assessed via Nissl staining, while\n                      <jats:italic>Sirt1<\/jats:italic>\n                      and\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      gene expression levels were quantified by RT\u2010qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      6\u2010OHDA lesioning produced marked reductions in locomotor activity, grip strength, and rotarod performance, accompanied by significant neuronal loss in the VTA and dysregulated\n                      <jats:italic>Sirt1\/Lingo\u20101<\/jats:italic>\n                      expression. Treatment with VitD3 or resveratrol alone partially improved motor performance and reduced neuronal loss, whereas the combination therapy produced the most pronounced neuroprotection. Co\u2010administration of VitD3 and resveratrol normalized\n                      <jats:italic>Sirt1<\/jats:italic>\n                      expression, suppressed\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      upregulation, and preserved neuronal morphology in the VTA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Combined treatment with VitD3 and resveratrol mitigates motor deficits and neurodegeneration in 6\u2010OHDA\u2010lesioned mice which was associated with activation of\n                      <jats:italic>Sirt1<\/jats:italic>\n                      and suppression of\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      . The results suggest the therapeutic potential of targeting the\n                      <jats:italic>Sirt1<\/jats:italic>\n                      and\n                      <jats:italic>Lingo\u20101<\/jats:italic>\n                      signaling pathways via nutraceutical interventions as a disease\u2010modifying strategy in PD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71673","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:21:44Z","timestamp":1786954904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Vitamin D and Resveratrol Treatment Attenuates Motor Deficits and Neurodegeneration in a 6\u2010OHDA Mouse Model of Parkinson's Disease in Male Mice: A Focus on Sirt1 and Lingo\u20101 Pathways in the Ventral Tegmental 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Office Rafsanjan University of Medical Sciences  Rafsanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynab","family":"Pirmoradi","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center Torbat Heydariyeh University of Medical Sciences  Torbat Heydariyeh Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Shabani","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman 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