Catalpol enhanced physical exercise-mediated brain functional improvement in post-traumatic stress disorder model via promoting adult hippocampal neurogenesis.

Lina Sun,Ruiqi Ye,Lei Liu,Lili Jiang,Chao Xi,Weiwei Zhang

doi:10.18632/aging.203313

Abstract

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by hyper-response to environmental cues as well as the associated depressive and cognitive dysfunctions. According to the key roles of hippocampus for cognitive and emotional regulation, improving hippocampal functions, particularly hippocampal neural plasticity, is the necessary pathway to attenuate the core symptoms of PTSD. The effects of the alternative therapies such as exercise and natural compounds to reduce PTSD symptoms and promote adult hippocampal neurogenesis have been widely demonstrated. However, what is the effect of combining the exercise with traditional Chinese medical compounds remains unknown. In current study, we evaluated the effects of catalpol, which showed the pro-neurogenic effects in previous report, in regulating exercise-mediated PTSD therapeutic effects. With behavioral tests, we found that catalpol treatment promoted the effects of exercise to reduce the response of mice to dangerous cues, and simultaneously enhanced the antidepressant and cognitive protection effects. Moreover, by immunofluorescence we identified that catalpol promoted exercise-mediated hippocampal neurogenesis by enhancing the neural differentiation and mature neuronal survive. We further found that the promote effects of catalpol to exercise-induced environmental hyper-response, antidepressant effects and cognitive protective effects were all compromised by blocking neurogenesis with temozolomide (TMZ). This result indicates that hippocampal neurogenesis is prerequisite for catalpol to promote exercise-mediated brain functional improvement in PTSD model. In conclusion, our research identified the new function of natural compounds catalpol to promote the exercise-mediated brain functional changes in PTSD model, which depend on its effect promoting adult hippocampal neurogenesis.

Highlights

Post-traumatic stress disorder (PTSD) is an anxiety disease that develops following frightening, stressful, or distressing life events, which affects the normal life and daily work of the subject with intense fear, helplessness, and stress
We have identified the effects of exercise in reduce PTSD associated depression and anxiety Akt-mediate regulating adult hippocampal neurogenesis [12]
Combination of catalpol enhanced the effects of treadmill to reduce PTSD symptoms We used the fear learning to mimic the development of the PTSD

Summary

Introduction

Post-traumatic stress disorder (PTSD) is an anxiety disease that develops following frightening, stressful, or distressing life events, which affects the normal life and daily work of the subject with intense fear, helplessness, and stress. The behavioral dysfunction of the PTSD mainly resulted from the dysregulation of the hippocampus, which plays the primary role in regulating learning and memory as well as the emotional functions [1, 2]. Adult hippocampal neurogenesis provides the structural plasticity to hippocampal networks to enhance the adaptability of animal to environmental stress [3]. The new formed neurons in DG region engage the hippocampus to separate the environmental cues and support the discrimination among the danger and safety surroundings [5]. Most of the stress response could affect the decreased adult hippocampal neurogenesis and thereby further decreased the pattern separation to environmental cues. The decreased adult hippocampal neurogenesis suppresses the learning and memory of the animals [8]. Improving the adult neurogenesis is the key to explore the therapeutic methods to PTSD

Methods

Results

Conclusion