{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:49Z","timestamp":1791355789381,"version":"4.3.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Sleep deprivation suppresses the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway, leading to oxidative stress, synaptic damage, and cognitive dysfunction. Glycosides of\n                      <jats:italic>Cistanche<\/jats:italic>\n                      (GCs) possess well-documented antioxidant and neuroprotective properties and have been reported to improve cognition in sleep-deprived animals, but the molecular mechanism remains unclear. We hypothesized that GCs alleviate sleep deprivation-induced cognitive dysfunction by activating the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixty male Sprague Dawley rats were randomly assigned to six groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f10): Control, Platform, Model, GCs, Control+GCs, and Estazolam (Est) groups. A 21-day sleep deprivation model was established using the modified multiple platform water method. Assessments included cognitive function by Morris water maze (MWM) test; Wake, non-rapid eye movement (NREM), rapid eye movement (REM), and total sleep time (TST) by Electroencephalogram (EEG); the serum levels of MDA, GSH-Px and SOD by ELISA, hippocampal CA1 neuronal morphology structure by Nissl staining and transmission electron microscopy (TEM), and the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway and synaptic related proteins were detected by Western blot. In an additional cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f40), the SIRT1-specific inhibitor EX527 was used to validate the causal role of the pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the Control group, the Model group exhibited significantly prolonged escape latency, along with reduced the number of platform crossings and the percentage time in the target quadrant (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). The proportion of Wake significantly increased, while NREM, REM, and TST all significantly decreased (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). The serum level of MDA elevated, while GSH-Px and SOD activities markedly reduced (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Hippocampal CA1 neurons showed disorganized arrangement, decreased Nissl bodies, and mitochondrial damage. Moreover, the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway and synaptic related proteins significantly downregulated (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Nevertheless, GCs intervention ameliorated cognitive dysfunction, alleviated oxidative stress and neuronal damage, and upregulated the protein expression levels above mentioned (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Notably, these protective effects of GCs were abrogated by the SIRT1 inhibitor EX527.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GCs inhibited oxidative stress damage and improved synaptic plasticity, and thereby alleviated sleep deprivation induced cognitive dysfunction by activating the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1945359","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:53:23Z","timestamp":1791352403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycosides of Cistanche improve cognitive dysfunction in sleep-deprived model rats by activating the SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway"],"prefix":"10.3389","volume":"19","author":[{"given":"Qiang","family":"Li","sequence":"first","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine, Baotou Medical College","place":["Baotou, China"]},{"name":"Department of Human Anatomy, Baotou Medical College","place":["Baotou, China"]},{"name":"Key Laboratory of Human Anatomy at Universities of Inner Mongolia Autonomous Region, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Baotou Central Hospital","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Huo","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine, Baotou Medical College","place":["Baotou, China"]},{"name":"Department of Human Anatomy, Baotou Medical College","place":["Baotou, China"]},{"name":"Key Laboratory of Human Anatomy at Universities of Inner Mongolia Autonomous Region, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine, Baotou Medical College","place":["Baotou, China"]},{"name":"Department of Human Anatomy, Baotou Medical College","place":["Baotou, China"]},{"name":"Key Laboratory of Human Anatomy at Universities of Inner Mongolia Autonomous Region, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine, Baotou Medical College","place":["Baotou, China"]},{"name":"Department of Human Anatomy, Baotou Medical College","place":["Baotou, China"]},{"name":"Key Laboratory of Human Anatomy at Universities of Inner Mongolia Autonomous Region, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Forensic Medicine, Baotou Medical College","place":["Baotou, China"]},{"name":"Department of Human Anatomy, Baotou Medical College","place":["Baotou, China"]},{"name":"Key Laboratory of Human Anatomy at Universities of Inner Mongolia Autonomous Region, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.jgr.2019.01.009","article-title":"Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation","volume":"44","author":"Cao","year":"2020","journal-title":"J. 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