{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:52Z","timestamp":1790618272701,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sleep deprivation (SD) has been increasingly implicated in age\u2010related cognitive decline. However, the mechanisms linking SD duration to progressive disruption of glial homeostasis, synaptic vulnerability, and metabolic dysregulation remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed 12\u2010month\u2010old Thy1\u2010EGFP and Cx3CR1\u2010EGFP mice to investigate the effects of short\u2010term sleep deprivation (SSD) and long\u2010term sleep deprivation (LSD) on neuronal architecture, microglial morphology, and astrocytic homeostasis. Quantitative analyses included dendritic spine density, synaptic protein expression, glial morphological and transcriptional markers, and untargeted plasma metabolomics. The neuroprotective effects of D30, a novel small molecule compound, were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SSD induced relatively transient oxidative stress and glial suppression, whereas LSD led to sustained reductions in dendritic spine density, synaptic protein levels, and microglial\/astrocytic morphological complexity. LSD further disrupted mitochondrial metabolism, notably involving the TCA cycle, AMPK\u2010associated signaling, and lipid homeostasis. Treatment with D30 significantly ameliorated LSD\u2010induced deficits by preserving glial homeostatic features, restoring synaptic protein expression, maintaining dendritic spine density, and rebalancing systemic metabolism, ultimately improving cognitive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LSD impairs glial homeostatic integrity and synaptic stability in association with systemic metabolic dysfunction in middle\u2010aged mice. D30 effectively alleviates these impairments, highlighting its potential as a protective intervention for chronic SD\u2010related neurocognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71134","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:52:33Z","timestamp":1789048353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sleep Deprivation Induces Glial Dysfunction, Synaptic Loss, Metabolic Imbalance, and Cognitive Impairment in 12\u2010Month\u2010Old Mice: Protective Effects of\n                    <scp>D30<\/scp>"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-2810","authenticated-orcid":false,"given":"Xueyan","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Fujian Medical University  Fuzhou China"},{"name":"School of Basic Medical Sciences, Fujian Medical University 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