美国索尔克生物研究所Sung Han研究组发现小鼠惊恐样行为和躯体症状背后的脑桥中脑 PACAPergic通路。该研究于2024年1月4日发表于国际一流学术期刊《自然—神经科学》杂志上。

他们报告了垂体腺苷酸环化酶激活多肽(PACAP)表达神经元，在侧臂旁核突出到中缝背是关键的恐慌样行为和生理改变。这些神经元被致恐慌刺激激活，但在条件性恐惧和焦虑条件下被抑制。激活这些神经元会引发强烈的防御行为和快速的心肺功能增强，而不会产生厌恶记忆，而抑制它们则会减轻恐慌相关症状。

下游表达PACAP受体的中背神经元的化学发生或药理学抑制可消除恐慌样症状。因此，脑桥中脑PACAPergic通路可能是恐慌发生的中介，并且可能是治疗恐慌障碍的有希望的治疗靶点。

据悉，惊恐障碍的特征是无法控制的恐惧，并伴有躯体症状，这是它与其他焦虑症的区别。这些独特症状背后的神经机制尚不完全清楚。

附：英文原文

Title: A pontomesencephalic PACAPergic pathway underlying panic-like behavioral and somatic symptoms in mice

Author: Kang, Sukjae J., Kim, Jong-Hyun, Kim, Dong-Il, Roberts, Benjamin Z., Han, Sung

Issue&Volume: 2024-01-04

Abstract: Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.

DOI: 10.1038/s41593-023-01504-3

Source: https://www.nature.com/articles/s41593-023-01504-3