{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:49:44Z","timestamp":1789145384572,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>G1 is a specific agonist of G protein\u2010coupled estrogen receptor 1 (GPER1), which binds and activates GPER1 to exert various neurological functions. However, the preventive effect of G1 on post\u2010traumatic stress disorder (PTSD) and its mechanisms are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the protective effect of G1 against synaptic and mitochondrial impairments and to investigate the mechanism of G1 to improve PTSD from brain\u2010derived neurotrophic factor (BDNF)\/tyrosine kinase receptor B (TrkB) signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study initially detected GPER1 expression in the hippocampus of single prolonged stress (SPS) mice, utilizing both Western blot and immunofluorescence staining. Subsequently, the effects of G1 on PTSD\u2010like behaviors, synaptic, and mitochondrial functions in SPS mice were investigated. Additionally, the involvement of BDNF\/TrkB signaling involved in the protection was further confirmed using GPER1 antagonist and TrkB inhibitor, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of GPER1 was reduced in the hippocampus of SPS mice, and G1 treatment given for 14 consecutive days significantly improved PTSD\u2010like behaviors in SPS mice compared with model group. Electrophysiological local field potential (LFP) results showed that G1 administration for 14 consecutive days could reverse the abnormal changes in the gamma oscillation in the CA1 region of SPS mice. Meanwhile, G1 administration for 14 consecutive days could significantly improve the abnormal expression of synaptic proteins, increase the expression of mitochondria\u2010related proteins, increase the number of synapses in the hippocampus, and ameliorate the damage of hippocampal mitochondrial structure in SPS mice. In addition, G15 (GPER1 inhibitor) and ANA\u201012 (TrkB inhibitor) blocked the ameliorative effects of G1 on PTSD\u2010like behaviors and aberrant expression of hippocampal synaptic and mitochondrial proteins in SPS mice and inhibited the reparative effects of G1 on structural damage to hippocampal mitochondria, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>G1 improved PTSD\u2010like behaviors in SPS mice, possibly by increasing hippocampal GPER1 expression and promoting BDNF\/TrkB signaling to repair synaptic and mitochondrial functional impairments. This study would provide critical mechanism for the prevention and treatment of PTSD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14855","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T03:48:52Z","timestamp":1720756132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activation of <scp>GPER1<\/scp> by <scp>G1<\/scp> prevents <scp>PTSD<\/scp>\u2010like behaviors in mice: Illustrating the mechanisms from <scp>BDNF<\/scp>\/<scp>TrkB<\/scp> to mitochondria and synaptic connection"],"prefix":"10.1111","volume":"30","author":[{"given":"Lixia","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Key Laboratory of Molecular Biology (Brain diseases) Anhui University of Chinese Medicine  Hefei 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