Abstract

BackgroundPost-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated.MethodsWe used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints.ResultsThe stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus.ConclusionsThis study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.

Highlights

  • Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflamma‐ tory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors

  • Electroa‐ cupuncture (EA) stimulation at the Baihui (GV 20) and Dazhui (GV 14) acupoints improves Repeated social defeat stress (RSDS)‐induced social avoidance C57BL/6 mice were individually anesthetized via a nose mask, and treated with EA at the following acupoints: Dazhui (GV14) and Baihui (GV20), or bilateral Tianzong (SI11) (Fig. 1A)

  • RSDS mice treated with sham stimulation, like the RSDS group, spent less time interacting when a target was present compared with the control group

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Summary

Introduction

Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflamma‐ tory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Post-traumatic stress disorder (PTSD), a common consequence of trauma, is a trauma and stressor-related disorder caused by exposure to severe traumatic events [1]. The clinical hallmarks of PTSD include avoidance of trauma reminders, re-experiencing a traumatic event, arousal, and hyperarousal symptoms. Repeated social defeat stress (RSDS) is a psychosocial stress animal model that induces symptoms of PTSD, such as emotional change and anxiety-like behavior [6, 7]. Our recent studies demonstrated that mice subjected to RSDS led to symptoms of PTSD, including social avoidance and anxiety-like behaviors [10, 11]

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