Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, JAPAN.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, JAPAN.
Med Sci Sports Exerc. 2024 Feb 1;56(2):221-229. doi: 10.1249/MSS.0000000000003312. Epub 2023 Sep 12.
Growing concern exists worldwide about stress-related mental disorders, such as posttraumatic stress disorder (PTSD), often linked to hippocampal dysfunctions. Recognizing this connection, regular light-intensity exercise (LIE)-such as yoga, walking, or slow jogging-may offer a solution. Easily accessible even to vulnerable individuals, LIE has been found to enhance hippocampus-based cognitive functions through the stimulation of neurotrophic factors like brain-derived neurotrophic factor (BDNF). A prior study that demonstrated BDNF's role in extinguishing original fear memory further leads us to propose that a consistent LIE training might drive fear extinction learning, offering potential therapeutic benefits through BDNF signaling.
Eleven-week-old Wistar rats underwent 4 wk of training under conditions of sedentary, LIE, or moderate-intensity exercise (MOE) after contextual or auditory fear conditioning. Subsequently, fear extinction tests were performed. We then administered intraperitoneal (i.p.) ANA-12, a selective antagonist of tropomyosin receptor kinase B (TrkB), or a vehicle to explore the role of BDNF signaling in exercise-induced fear extinction among the LIE rats. Following the regular exercise training, further fear extinction tests were conducted, and hippocampal protein analysis was performed using Western blotting.
Both LIE and MOE over 4 wk accelerated hippocampus-associated contextual fear extinction compared with sedentary. In addition, 4 wk of LIE with i.p. administered vehicle increased hippocampal BDNF and TrkB protein levels. In contrast, i.p. ANA-12 administration fully blocked the LIE-enhanced protein levels and its effect on contextual fear extinction.
Our findings reveal that LIE regimen promotes fear extinction learning, at least partially tied to hippocampal BDNF-TrkB signaling. This suggests that even regular light exercise could alleviate the excessive fear response in anxiety disorders and PTSD, providing hope for those affected.
全世界越来越关注与压力相关的精神障碍，如创伤后应激障碍（PTSD），其通常与海马功能障碍有关。鉴于这种联系，有规律的低强度运动（LIE），如瑜伽、散步或慢跑，可能是一种解决方案。LIE 很容易被包括弱势群体在内的人所接受，它已被发现通过刺激神经营养因子，如脑源性神经营养因子（BDNF），增强基于海马的认知功能。先前的一项研究表明 BDNF 在消除原始恐惧记忆中的作用，这进一步促使我们提出，持续的 LIE 训练可能会促进恐惧消除学习，通过 BDNF 信号传递提供潜在的治疗益处。
11 周龄 Wistar 大鼠在条件性或听觉恐惧条件作用后进行 4 周的静坐、LIE 或中等强度运动（MOE）训练。随后进行恐惧消退测试。然后我们给 LIE 大鼠腹腔内（i.p.）注射 ANA-12，一种选择性的原肌球蛋白受体激酶 B（TrkB）拮抗剂，或载体，以探索 BDNF 信号在运动诱导的恐惧消退中的作用。在常规运动训练后，进一步进行恐惧消退测试，并使用 Western blot 进行海马蛋白分析。
4 周的 LIE 和 MOE 均加速了与海马相关的情境恐惧消退，而静坐则没有。此外，4 周的 LIE 加 i.p. 给予载体增加了海马 BDNF 和 TrkB 蛋白水平。相反，i.p. ANA-12 给药完全阻断了 LIE 增强的蛋白水平及其对情境恐惧消退的影响。
我们的研究结果表明，LIE 方案促进了恐惧消退学习，至少部分与海马 BDNF-TrkB 信号有关。这表明，即使是有规律的低强度运动也可以减轻焦虑障碍和 PTSD 中的过度恐惧反应，为患者带来希望。
