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夏枯草改善大鼠淀粉样蛋白β诱导的脑网络紊乱:电生理和行为学研究

Teucrium Polium ameliorates amyloid β-induced brain network disorders in rats: electrophysiological and behavioral studies.

作者信息

Simonyan Karen, Darbinyan Lilit, Hambardzumyan Lilia, Manukyan Larisa, Chavushyan Vergine

机构信息

Neuroendocrine Relationships Lab, Orbeli Institute of Physiology NAS RA, Yerevan, 0028, Armenia.

Sensorimotor Integration Lab, Orbeli Institute of Physiology NAS RA, Yerevan, 0028, Armenia.

出版信息

BMC Complement Med Ther. 2025 Mar 27;25(1):116. doi: 10.1186/s12906-024-04715-8.

Abstract

Synaptic failure in specific cholinergic networks in rat brains has been implicated in amyloid β-induced neurodegeneration. Teucrium polium is a promising candidate for drug development against Alzheimer's disease (AD) and similar disorders. However, the protective effect of Teucrium polium against amyloid β-induced impairment of short-term synaptic plasticity is still poorly understood. In this study, we used in vivo extracellular single-unit recordings to investigate the preventive efficacy of Teucrium polium on Aβ(25-35)-induced aberrant neuronal activity in the hippocampus and basolateral amygdala of rats, in response to high-frequency stimulation of the cholinergic nucleus basalis magnocellularis (NBM). After 12 weeks of intracerebroventricular administration of Aβ(25-35), alterations such as decreased excitatory responses and increased inhibitory synaptic activity were observed in the NBM-hippocampus and NBM-basolateral amygdala cholinergic circuits. Treatment with Teucrium polium improved the balance of excitatory and inhibitory responses by modulating synaptic transmission strength and restoring short-term plasticity. Acute injection of a therapeutic dose of Teucrium temporarily inhibited spiking activity in single NBM neurons. Open field tests revealed that amyloid-injected rats displayed anxiety and reduced exploratory drive. Treatment with Teucrium polium improved these behaviors, reducing anxiety and increasing exploration. Teucrium polium mitigated amyloid β-induced alterations in cholinergic circuits by enhancing the adaptive capacity of short-term synaptic plasticity. These findings suggest that Teucrium polium could serve as a preventive strategy to delay the progression of cholinergic neurodegeneration.

摘要

大鼠大脑中特定胆碱能网络的突触功能障碍与β-淀粉样蛋白诱导的神经退行性变有关。夏香薄荷是开发抗阿尔茨海默病(AD)及类似疾病药物的一个有前景的候选药物。然而,夏香薄荷对β-淀粉样蛋白诱导的短期突触可塑性损伤的保护作用仍知之甚少。在本研究中,我们使用体内细胞外单单位记录技术,来研究夏香薄荷对大鼠海马体和基底外侧杏仁核中由Aβ(25-35)诱导的异常神经元活动的预防效果,该活动是对胆碱能大细胞基底核(NBM)高频刺激的反应。在脑室内注射Aβ(25-35)12周后,在NBM-海马体和NBM-基底外侧杏仁核胆碱能回路中观察到兴奋性反应降低和抑制性突触活动增加等变化。夏香薄荷治疗通过调节突触传递强度和恢复短期可塑性,改善了兴奋性和抑制性反应的平衡。急性注射治疗剂量的夏香薄荷可暂时抑制单个NBM神经元的放电活动。旷场试验显示,注射淀粉样蛋白的大鼠表现出焦虑和探索驱动力降低。夏香薄荷治疗改善了这些行为,减轻了焦虑并增加了探索行为。夏香薄荷通过增强短期突触可塑性的适应能力,减轻了β-淀粉样蛋白诱导的胆碱能回路变化。这些发现表明,夏香薄荷可作为一种预防策略,来延缓胆碱能神经退行性变的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf6/11948851/2cab889026f4/12906_2024_4715_Fig2_HTML.jpg

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