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Abstract：
BACKGROUND: G1 is a specific agonist of G protein-coupled estrogen receptor 1 (GPER1), which binds and activates GPER1 to exert various neurological functions. However, the preventive effect of G1 on post-traumatic stress disorder (PTSD) and its mechanisms are unclear.
OBJECTIVE: To evaluate the protective effect of G1 against synaptic and mitochondrial impairments and to investigate the mechanism of G1 to improve PTSD from brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling.
METHODS: 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-like 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.
RESULTS: The expression of GPER1 was reduced in the hippocampus of SPS mice, and G1 treatment given for 14 consecutive days significantly improved PTSD-like 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-related 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-12 (TrkB inhibitor) blocked the ameliorative effects of G1 on PTSD-like 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.
CONCLUSIONS: G1 improved PTSD-like 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.
OBJECTIVE: To evaluate the protective effect of G1 against synaptic and mitochondrial impairments and to investigate the mechanism of G1 to improve PTSD from brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling.
METHODS: 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-like 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.
RESULTS: The expression of GPER1 was reduced in the hippocampus of SPS mice, and G1 treatment given for 14 consecutive days significantly improved PTSD-like 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-related 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-12 (TrkB inhibitor) blocked the ameliorative effects of G1 on PTSD-like 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.
CONCLUSIONS: G1 improved PTSD-like 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.
摘要：
背景：G1是G蛋白偶联雌激素受体1（GPER1）的特异性激动剂，它结合并激活GPER1以发挥各种神经功能。然而,G1对创伤后应激障碍（PTSD）的预防作用及其机制尚不清楚。
目的：评估G1对突触和线粒体损伤的保护作用，并探讨G1通过脑源性神经营养因子（BDNF）/酪氨酸激酶受体B（TrkB）信号通路改善PTSD的机制。
方法：这项研究最初检测了单次延长应激（SPS）小鼠海马中的GPER1表达，利用蛋白质印迹和免疫荧光染色。随后，G1对PTSD样行为的影响，突触，研究了SPS小鼠的线粒体功能。此外,使用GPER1拮抗剂和TrkB抑制剂进一步证实了BDNF/TrkB信号参与保护，分别。
结果：SPS小鼠海马中GPER1的表达降低，与模型组相比，连续14天给予G1治疗显着改善了SPS小鼠的PTSD样行为。电生理局部场电位(LFP)结果表明，连续14天G1给药可以逆转SPS小鼠CA1区γ振荡的异常变化。同时,G1连续给药14天能显著改善突触蛋白的异常表达，增加线粒体相关蛋白的表达，增加海马中突触的数量，改善SPS小鼠海马线粒体结构的损伤。此外,G15（GPER1抑制剂）和ANA-12（TrkB抑制剂）阻断G1对SPS小鼠PTSD样行为和海马突触和线粒体蛋白异常表达的改善作用，并抑制G1对海马线粒体结构损伤的修复作用。分别。
结论：G1改善了SPS小鼠的PTSD样行为，可能通过增加海马GPER1表达和促进BDNF/TrkB信号传导来修复突触和线粒体功能损伤。这项研究将为PTSD的预防和治疗提供关键机制。
目的：评估G1对突触和线粒体损伤的保护作用，并探讨G1通过脑源性神经营养因子（BDNF）/酪氨酸激酶受体B（TrkB）信号通路改善PTSD的机制。
方法：这项研究最初检测了单次延长应激（SPS）小鼠海马中的GPER1表达，利用蛋白质印迹和免疫荧光染色。随后，G1对PTSD样行为的影响，突触，研究了SPS小鼠的线粒体功能。此外,使用GPER1拮抗剂和TrkB抑制剂进一步证实了BDNF/TrkB信号参与保护，分别。
结果：SPS小鼠海马中GPER1的表达降低，与模型组相比，连续14天给予G1治疗显着改善了SPS小鼠的PTSD样行为。电生理局部场电位(LFP)结果表明，连续14天G1给药可以逆转SPS小鼠CA1区γ振荡的异常变化。同时,G1连续给药14天能显著改善突触蛋白的异常表达，增加线粒体相关蛋白的表达，增加海马中突触的数量，改善SPS小鼠海马线粒体结构的损伤。此外,G15（GPER1抑制剂）和ANA-12（TrkB抑制剂）阻断G1对SPS小鼠PTSD样行为和海马突触和线粒体蛋白异常表达的改善作用，并抑制G1对海马线粒体结构损伤的修复作用。分别。
结论：G1改善了SPS小鼠的PTSD样行为，可能通过增加海马GPER1表达和促进BDNF/TrkB信号传导来修复突触和线粒体功能损伤。这项研究将为PTSD的预防和治疗提供关键机制。
