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The progression of AD severely affects late\u2010phase long\u2010term potentiation (L\u2010LTP), which is essential for long\u2010term memory consolidation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We have previously demonstrated the beneficial effects of acute restraint stress (ARS) on hippocampal LTP in AD mouse models. This study aimed to verify the effects and potential mechanisms of ARS on the maintenance of hippocampal L\u2010LTP in two AD mouse models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>5xFAD and Tg2576 mice underwent a 30\u2010min body immobilization protocol to induce ARS, followed by electrophysiological recordings of L\u2010LTP (&gt;\u20093\u2009h) in the CA1 region of thehippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ARS\u2010exposed group exhibited significantly enhanced L\u2010LTP compared to the control group. Maintenance of L\u2010LTP requires new protein synthesis and signaling via the mammalian target of rapamycin (mTOR) pathway. Our findings revealed that ARS increased hippocampal adenosine triphosphate (ATP) production and reduced AMPK activity. Inactivation of AMPK and subsequent activation of the mTOR pathway were strongly associated with the ARS\u2010facilitated enhancement of L\u2010LTP. Furthermore, our experiments using the mTOR inhibitor rapamycin demonstrated that it effectively prevented the enhancement of L\u2010LTP following ARS, underscoring the pivotal role of mTOR in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ARS may significantly modify AMPK activation and mTOR regulation in L\u2010LTP, potentially triggering the mechanisms of long\u2010term memory consolidation in AD mouse model mice. Identifying these underlying mechanisms could help promote the development of novel pharmaceutical agents for the treatment of AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70335","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:54:21Z","timestamp":1742356461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acute Restraint Stress Induces Long\u2010Lasting Synaptic Enhancement by Inhibiting <scp>AMPK<\/scp> Activation in <scp>AD<\/scp> Model Mice"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9372-4897","authenticated-orcid":false,"given":"Ming","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health Health Science Center, Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyuan","family":"Jin","sequence":"additional","affiliation":[{"name":"The First 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