Paeonol mitigates chronic stress-induced amygdalar neuronal damage through glycogen synthase kinase-3β/calcineurin axis regulation of synaptic plasticity.

IF 1.6 4区 医学 Q4 NEUROSCIENCES
Qiang Li, Xili Yan, Yingdi Zhao, Zhiliang Xu, Xiuling Zhu
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引用次数: 0

Abstract

Objective: This study aimed to elucidate the neuroprotective mechanisms of paeonol in ameliorating chronic stress-induced amygdala neuronal injury via modulation of the glycogen synthase kinase-3β (GSK3β)/calcineurin signaling pathway. Paeonol, a polyphenolic compound from Moutan Cortex, exhibits therapeutic effects. Studies show it alleviates lipopolysaccharide-induced depression-like behaviors in mice, though its mechanisms remain unclear.

Methods: Forty-eight Sprague-Dawley rats were divided into four groups: control, chronic unpredictable mild stress (CUMS) model, low-dose paeonol (25 mg/kg), and high-dose paeonol (80 mg/kg). Paeonol was administered intragastrically 1-week post-CUMS induction for 4 weeks. Behavioral tests assessed depression-like behaviors. Neuronal morphology was evaluated via hematoxylin and eosin, Nissl, and Golgi staining, while western blot quantified cofilin1, p-cofilin1, GSK3β, and calcineurin expression.

Results: CUMS rats exhibited depressive-like behaviors, neuronal nuclear pyknosis, interstitial edema, hyperchromatic cytoplasm, and reduced Nissl body integrity. Golgi staining revealed increased dendritic complexity and spine density. CUMS upregulated p-cofilin1 and GSK3β while downregulating total cofilin1 and calcineurin. Paeonol treatment alleviated depressive behaviors, reduced neuronal damage, and normalized dendritic complexity and spine density. Molecularly, paeonol suppressed p-cofilin1 and GSK3β expression while restoring cofilin1 and calcineurin levels.

Conclusion: Chronic stress induces dendritic hypertrophy and spine hyperplasticity, contributing to depressive phenotypes. Paeonol counteracts these effects, likely by modulating the GSK3β/calcineurin pathway, highlighting its therapeutic potential for stress-related neuronal injury.

丹皮酚通过糖原合成酶激酶-3β/钙调磷酸酶轴调节突触可塑性减轻慢性应激诱导的杏仁核神经元损伤。
目的:探讨丹皮酚通过调节糖原合成酶激酶-3β (GSK3β)/钙调磷酸酶信号通路改善慢性应激性杏仁核神经元损伤的神经保护机制。丹皮酚是牡丹皮中的一种多酚类化合物,具有治疗作用。研究表明,它减轻了脂多糖引起的小鼠抑郁样行为,尽管其机制尚不清楚。方法:48只Sprague-Dawley大鼠分为对照组、慢性不可预知轻度应激(CUMS)模型组、低剂量丹皮酚(25 mg/kg)组和高剂量丹皮酚(80 mg/kg)组。在cums诱导后1周灌胃丹皮酚4周。行为测试评估类似抑郁的行为。通过苏木精和伊红染色、尼氏染色和高尔基染色评估神经元形态,western blot定量检测cofilin1、p-cofilin1、GSK3β和钙调神经磷酸酶的表达。结果:CUMS大鼠表现出抑郁样行为,神经元核固缩,间质水肿,细胞质深染,尼氏体完整性降低。高尔基染色显示树突复杂性和脊柱密度增加。CUMS上调p-cofilin1和GSK3β,下调总cofilin1和钙调神经磷酸酶。丹皮酚治疗减轻了抑郁行为,减少了神经元损伤,使树突复杂性和脊柱密度正常化。从分子上看,丹皮酚抑制了p-cofilin1和GSK3β的表达,同时恢复了cofilin1和钙调磷酸酶的水平。结论:慢性应激诱导树突肥大和脊柱超可塑性,导致抑郁表型。丹皮酚可能通过调节GSK3β/钙调神经磷酸酶通路来抵消这些影响,突出其治疗应激相关神经元损伤的潜力。
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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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