Eid Fady, El Ahmad Perla, Khoury Reine, El Masri Diala, El Zoghby Yara, Sahlloul Yasmin, Fadel Joanna, Haddad Zena, Mezher Amar, Ghayad Litsa Maria, El Sabbagh Yorgo, Gerges Lea, Lakis Mahmoud, Sahyoun Christopher, El Khoury Ghinwa, Stephan Joseph S, Sleiman Sama F
Biological Sciences Program, Department of Natural Sciences, Lebanese American University, Lebanon, Byblos, Lebanon.
School of Medicine, Lebanese American University, Lebanon, Byblos, Lebanon.
Biol Psychiatry Glob Open Sci. 2025 Mar 3;5(3):100477. doi: 10.1016/j.bpsgos.2025.100477. eCollection 2025 May.
Depression poses a significant societal burden, necessitating effective treatment options. Conventional approaches often fall short, highlighting the need for alternatives. Exercise has emerged as a promising nonpharmacological strategy for improving mental health outcomes. Exercise promotes memory recall and alleviates depression by modulating BDNF (brain-derived neurotrophic factor) expression. The effects of exercise on BDNF are influenced by circulatory metabolites known as exercise factors.
Associative and spatial memory were evaluated in mice receiving α-ketoglutarate (aKG) and in exercise mice given a glutaminase inhibitor. To prevent and treat depression-like behaviors, male mice underwent daily defeat sessions by a CD1 aggressor for 10 days. Behavior was assessed on day 11 using social interaction and open-field tests. Mice received aKG for 5 days prior to the stress paradigm or as treatment for 14 days following the stress paradigm, after which social behavior was reassessed. BDNF signaling was examined via Western blots.
aKG was identified as a metabolite released into the bloodstream following exercise in male mice. aKG was shown to mediate the positive effects of exercise on spatial learning and memory formation. aKG was also shown to have prophylactic and antidepressant effects in a chronic social defeat stress model of depression.
aKG acts as a prophylactic and antidepressant to effectively counteract social avoidance behaviors by modulating BDNF levels in the hippocampus and nucleus accumbens.
抑郁症带来了巨大的社会负担，因此需要有效的治疗方案。传统方法往往效果不佳，这凸显了寻找替代方法的必要性。运动已成为一种有前景的非药物策略，可改善心理健康状况。运动通过调节脑源性神经营养因子（BDNF）的表达来促进记忆回忆并减轻抑郁。运动对BDNF的影响受称为运动因子的循环代谢物的影响。
对接受α-酮戊二酸（aKG）的小鼠以及给予谷氨酰胺酶抑制剂的运动小鼠的联想记忆和空间记忆进行评估。为了预防和治疗类似抑郁的行为，雄性小鼠每天接受来自CD1攻击者的失败训练，持续10天。在第11天使用社交互动和旷场试验评估行为。小鼠在应激范式之前接受aKG治疗5天，或在应激范式之后作为治疗持续14天，之后重新评估社交行为。通过蛋白质免疫印迹法检测BDNF信号传导。
aKG被确定为雄性小鼠运动后释放到血液中的一种代谢物。aKG被证明可介导运动对空间学习和记忆形成的积极影响。aKG在慢性社会挫败应激抑郁模型中也显示出预防和抗抑郁作用。
aKG作为一种预防和抗抑郁剂，通过调节海马体和伏隔核中的BDNF水平，有效对抗社交回避行为。
