Accelerated Fear Extinction by Regular Light-Intensity Exercise: A Possible Role of Hippocampal BDNF-TrkB Signaling.

ABSTRACT

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.