{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T17:17:38Z","timestamp":1781371058885,"version":"3.54.1"},"reference-count":77,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671316"],"award-info":[{"award-number":["81671316"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gestational intermittent hypoxia (GIH), which serves as a model for obstructive sleep apnea (OSA), is associated with adverse maternal and neonatal outcomes, especially cognitive impairments in offspring. Growing evidence supports that the anti\u2010inflammatory actions of melatonin significantly influence the peripartum environment and contribute to the mitigation of neurodegeneration. However, the full impact of GIH on offspring cognition and the molecular mechanisms by which melatonin modulates these effects remain uncertain. Thus, in this study, we explored the neurobiological changes in GIH\u2010exposed offspring and the mechanism underlying maternal melatonin supplementation in preventing these alterations using a murine model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL\/6J mice were exposed to GIH between gestational Days 15 and 21. Concurrently, dams received either vehicle or melatonin. The Morris water maze test was employed to evaluate offspring cognitive function, after which the offspring were euthanized at 2 months of age. The hippocampal levels of glial markers (ionized calcium\u2010binding adapter molecule 1 [Iba\u20101], glial fibrillary acidic protein [GFAP]), NOD\u2010like receptor thermal protein domain\u2010associated protein 3 [NLRP3], nuclear factor\u2010kappa B [NF\u2010\u03baB], tight\u2010junction proteins (zonula occludens\u20101 [ZO\u20101], occludin), and synaptic plasticity\u2010related proteins (brain\u2010derived neurotrophic factor [BDNF], tropomyosin receptor kinase B [TrkB], postsynaptic density protein 95 [PSD\u201095], synaptophysin [SYN]) were quantified by enzyme\u2010linked immunosorbent assay and western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maternal melatonin supplementation significantly attenuated learning and memory impairments, reduced the protein levels of Iba\u20101 and GFAP by suppressing NLRP3\/NF\u2010\u03baB signaling, and elevated those of ZO\u20101, occludin, BDNF, TrkB, PSD\u201095, and SYN. Additionally, melatonin mitigated inflammatory responses, glial cell activation, blood\u2013brain barrier (BBB) leakage, and synaptic dysfunction induced by GIH in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrated that GIH\u2010exposed mice exhibit cognitive deficits, alongside neuroinflammatory responses, leading to inflammasome activation, glial reactivity, BBB breakdown, and synaptic deficits. However, melatonin exerted significant protective effects against these deleterious effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71321","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:47:54Z","timestamp":1775018874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Potential Functions and Beneficial Effects of Melatonin on Cognitive Impairment, Neuroinflammation, Blood\u2013Brain Barrier Leakage, and Synaptic Dysfunction in the Offspring of Mice Exposed to Gestational Intermittent Hypoxia"],"prefix":"10.1002","volume":"16","author":[{"given":"Xue\u2010Yan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology the First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"Department of Neurology Anhui Public Health Clinical Center  Hefei Anhui China"},{"name":"Department of Neurology (Sleep Disorders) the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Zhoug","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Paediatrics the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology (Sleep Disorders) the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology (Sleep Disorders) the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Kun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology (Sleep Disorders) the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Hai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology (Sleep Disorders) the Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology the First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"Department of Neurology Anhui Public Health Clinical Center  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10071020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0030\u20102019"},{"issue":"3","key":"e_1_2_11_4_1","first-page":"280","article-title":"Therapeutic Application of Melatonin in Mild Cognitive Impairment","volume":"1","author":"Cardinali D. 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