{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:56:37Z","timestamp":1791402997101,"version":"4.3.3"},"reference-count":69,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571229"],"award-info":[{"award-number":["31571229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022YB012"],"award-info":[{"award-number":["2022YB012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["R01 MH121454"],"award-info":[{"award-number":["R01 MH121454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["R01 DA047269"],"award-info":[{"award-number":["R01 DA047269"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Universities Scientific Fund","award":["31571229"],"award-info":[{"award-number":["31571229"]}]},{"name":"Chinese Universities Scientific Fund","award":["2022YB012"],"award-info":[{"award-number":["2022YB012"]}]},{"name":"Chinese Universities Scientific Fund","award":["R01 MH121454"],"award-info":[{"award-number":["R01 MH121454"]}]},{"name":"Chinese Universities Scientific Fund","award":["R01 DA047269"],"award-info":[{"award-number":["R01 DA047269"]}]},{"name":"NIH","award":["31571229"],"award-info":[{"award-number":["31571229"]}]},{"name":"NIH","award":["2022YB012"],"award-info":[{"award-number":["2022YB012"]}]},{"name":"NIH","award":["R01 MH121454"],"award-info":[{"award-number":["R01 MH121454"]}]},{"name":"NIH","award":["R01 DA047269"],"award-info":[{"award-number":["R01 DA047269"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Physical exercise improves memory and cognition in physiological aging and Alzheimer\u2019s disease (AD), but the mechanisms remain poorly understood. Here, we test the hypothesis that A\u03b2 oligomer accumulation, neuroinflammation, and glial cell activation may lead to disruption of synaptic transmission in the prefrontal cortex of 3 \u00d7 Tg-AD Mice, resulting in impairment of learning and memory. On the other hand, treadmill exercise could prevent the pathogenesis and exert neuroprotective effects. Here, we used immunohistochemistry, western blotting, enzyme-linked immunosorbent assay, and slice electrophysiology to analyze the levels of GSK3\u03b2, A\u03b2 oligomers (A\u03b2 dimers and trimers), pro-inflammatory cytokines (IL-1\u03b2, IL-6, and TNF\u03b1), the phosphorylation of CRMP2 at Thr514, and synaptic currents in pyramidal neurons in the prefrontal cortex. We show that 12-week treadmill exercise beginning in three-month-old mice led to the inhibition of GSK3\u03b2 kinase activity, decreases in the levels of A\u03b2 oligomers, pro-inflammatory cytokines (IL-1\u03b2, IL-6, and TNF\u03b1), and the phosphorylation of CRMP2 at Thr514, reduction of microglial and astrocyte activation, and improvement of excitatory and inhibitory synaptic transmission of pyramidal neurons in the prefrontal cortex of 3 \u00d7 Tg-AD Mice. Thus, treadmill exercise reduces neuroinflammation, glial cell activation and improves synaptic transmission in the prefrontal cortex in 3 \u00d7 Tg-AD mice, possibly related to the inhibition of GSK3\u03b2 kinase activity.<\/jats:p>","DOI":"10.3390\/ijms232012655","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:40:36Z","timestamp":1666586436000},"page":"12655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Treadmill Exercise Reduces Neuroinflammation, Glial Cell Activation and Improves Synaptic Transmission in the Prefrontal Cortex in 3 \u00d7 Tg-AD Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Lianwei","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Exercise Physiology, Guangzhou Sport University, Guangzhou 510500, China"},{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"},{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Cai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boya","family":"Gu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-1674","authenticated-orcid":false,"given":"Xiaojie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-2520","authenticated-orcid":false,"given":"Vladislav","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-1504","authenticated-orcid":false,"given":"Qing-Song","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a005777","DOI":"10.1101\/cshperspect.a005777","article-title":"Synapses and Alzheimer\u2019s disease","volume":"4","author":"Sheng","year":"2012","journal-title":"Cold Spring Harb. 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