Sinapic acid balances the excitatory and inhibitory neurotransmitter systems to mitigate post-traumatic stress disorder-like behaviors

IF 6.4 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2026-03-01 Epub Date: 2026-01-11 DOI:10.1016/j.lfs.2026.124201

Chang Hyeon Kong , Keontae Park , Ju Eun Han , Ho Jung Bae , Se Jin Park , Seo Yun Jung , Dong Hyun Kim , Jong Hoon Ryu

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引用次数: 0

Abstract

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Sinapic acid has been reported to be effective for anxiety as a GABA_A receptor agonist, and has been reported to improve cognitive impairment by modulating the GABA/glutamate ratio, but there are no reports associated with PTSD. In the present study, we investigated the effects of sinapic acid in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol.

We examined the therapeutic effects of sinapic acid on emotional and cognitive impairment in the SPS mouse model. We also explored the effects of sinapic acid on fear memory extinction. Western blot was employed to investigate how sinapic acid exerts its pharmacological activities.

Sinapic acid ameliorated PTSD-like behaviors in a SPS mouse model. Notably, in the case of cognitive dysfunction, paroxetine failed to improve, but sinapic acid restored cognitive function. Additionally, sinapic acid did not increase locomotor behavior, while paroxetine increased. Furthermore, sinapic acid normalized the overactivated GluN2B-containing NMDA receptor signaling pathway in the amygdala and the hypothalamus. The mitigation of fear memory deficits by sinapic acid was exerted by sub-effective dose of GluN2B-containing NMDA receptor antagonist and abolished by GABA_A receptor antagonist.

Our findings suggest that sinapic acid could serve as a potential therapeutic agent for PTSD by balancing excitatory and inhibitory neurotransmitter systems due to its action on GluN2B-containing NMDA receptors and GABA_A receptors.

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辛酸平衡兴奋性和抑制性神经递质系统，以减轻创伤后应激障碍样行为。

创伤后应激障碍（PTSD）是一种精神疾病，可能发生在经历过创伤的个体身上。据报道，Sinapic酸作为GABAA受体激动剂对焦虑有效，并通过调节GABA/谷氨酸比值改善认知障碍，但没有与PTSD相关的报道。在本研究中，我们研究了辛酸对单一延长应激（SPS）方案诱导的创伤后应激障碍小鼠模型的影响。我们在SPS小鼠模型中检测了辛酸对情绪和认知障碍的治疗作用。我们还探讨了辛酸对恐惧记忆消退的影响。Western blot法观察辛酸的药理作用。辛酸可改善SPS小鼠的ptsd样行为。值得注意的是，在认知功能障碍的情况下，帕罗西汀未能改善，但辛酸恢复了认知功能。此外，辛酸不增加运动行为，而帕罗西汀增加。此外，辛酸使杏仁核和下丘脑中过度激活的含glun2b的NMDA受体信号通路正常化。sinapic酸对恐惧记忆缺陷的缓解作用是通过亚有效剂量glun2b -含NMDA受体拮抗剂发挥作用，并被GABAA受体拮抗剂消除。我们的研究结果表明，辛酸可以作为一种潜在的治疗药物，通过平衡兴奋性和抑制性神经递质系统，由于其作用于glun2b -含NMDA受体和GABAA受体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.