岛叶通过GluA1受体和AC1参与调控大鼠头痛及相关焦虑行为*

Insula is involved in the regulation of headache and related anxiety behaviors in rats through GluA1 receptor and AC1.

摘要:

目的：通过大鼠模型明确岛叶是否参与偏头痛发病并探索其机制。方法：连续硬膜外注射炎症汤建立慢性偏头痛（chronic migraine, CM）大鼠模型。von-Frey纤维丝评估眶周机械阈值。通过旷场和高架十字迷宫实验观察动物焦虑行为。使用免疫印迹实验检测岛叶α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚型1-GluA1受体及腺苷酸环化酶1（Adenylate cyclase 1，AC1）的表达。通过双侧岛叶注射AC1抑制剂探索可能的机制。结果：连续炎症汤刺激硬脑膜可诱导大鼠产生偏头痛样头痛及焦虑行为。与对照组相比，CM组岛叶的c-Fos, GluA1及其磷酸化（p-GluA1-S845）和AC1的表达显著增加。岛叶注射AC1抑制剂可缓解大鼠的机械阈值和焦虑行为，降低岛叶AC1和GluA1表达量及p-GluA1-S845水平。结论：岛叶通过GluA1及AC1参与调控大鼠偏头痛样头痛及焦虑行为。

Abstract:

Objective: This study aims to determine the role of the insula in the pathogenesis of migraine and explore its underlying mechanisms through a rat model. Method: A chronic migraine (CM) rat model was established by continuous dural infusion of inflammatory soup. The periorbital mechanical threshold was assessed using von-Frey filaments. Anxiety behaviors in animals were observed through open field test and elevated plus maze test. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1-GluA1 receptor and adenylate cyclase 1 (AC1) in the insula was detected by western blot test. A potential mechanism was explored by injecting an AC1 inhibitor bilaterally into the insula. Results: Continuous inflammatory soup stimulation of the dura mater could induce migraine-like headache and anxiety behaviors in rats. Compared with the control group, the expression of c-Fos, GluA1, the phosphorylate of GluA1 (p-GluA1-S845), and AC1 in the insula of the CM group significantly increased. Injection of the AC1 inhibitor into the insula could alleviate mechanical threshold and anxiety behaviors in rats, and reduce the expression level of AC1, GluA1 and p-GluA1-S845 in the insula. Conclusion: The insula regulates migraine-like headache and anxiety behaviors in rats through GluA1 and AC1.