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陆清波, 孙剑飞, 杨屈杨, 蔡雯雯, 夏梦琴, 吴芳芳, 顾宁, 张志珺. 2020: 磁性纳米氧化铁药物介导的脑磁刺激新策略可快速改善小鼠抑郁样行为. 动物学研究, 41(4): 381-394. DOI: 10.24272/j.issn.2095-8137.2020.076
引用本文: 陆清波, 孙剑飞, 杨屈杨, 蔡雯雯, 夏梦琴, 吴芳芳, 顾宁, 张志珺. 2020: 磁性纳米氧化铁药物介导的脑磁刺激新策略可快速改善小鼠抑郁样行为. 动物学研究, 41(4): 381-394. DOI: 10.24272/j.issn.2095-8137.2020.076
Qing-Bo Lu, Jian-Fei Sun, Qu-Yang Yang, Wen-Wen Cai, Meng-Qin Xia, Fang-Fang Wu, Ning Gu, Zhi-Jun Zhang. 2020: Magnetic brain stimulation using iron oxide nanoparticle-mediated selective treatment of the left prelimbic cortex as a novel strategy to rapidly improve depressive-like symptoms in mice. Zoological Research, 41(4): 381-394. DOI: 10.24272/j.issn.2095-8137.2020.076
Citation: Qing-Bo Lu, Jian-Fei Sun, Qu-Yang Yang, Wen-Wen Cai, Meng-Qin Xia, Fang-Fang Wu, Ning Gu, Zhi-Jun Zhang. 2020: Magnetic brain stimulation using iron oxide nanoparticle-mediated selective treatment of the left prelimbic cortex as a novel strategy to rapidly improve depressive-like symptoms in mice. Zoological Research, 41(4): 381-394. DOI: 10.24272/j.issn.2095-8137.2020.076

磁性纳米氧化铁药物介导的脑磁刺激新策略可快速改善小鼠抑郁样行为

Magnetic brain stimulation using iron oxide nanoparticle-mediated selective treatment of the left prelimbic cortex as a novel strategy to rapidly improve depressive-like symptoms in mice

  • 摘要: 磁刺激极大地促进了神经科学的进步,其中高频(10 Hz)重复经颅磁刺激(rTMS)刺激左背外侧前额叶皮层(DLPFC)已于2008年获得美国食品药品监督管理局(FDA)的批准,用于治疗成人难治性抑郁。但目前rTMS仍然存在技术局限性,包括穿透力差,磁刺激聚焦精度不足,刺激深度有限等。特别是在小动物精神疾病模型中,即使最小的通用线圈也会刺激整个半球甚至整个大脑,无法做到精准定位,难以研究rTMS的神经调控机制等脑科学相关的重大科学问题。针对此问题,我们提出了利用获得中国FDA批准的超顺磁性纳米氧化铁(SPIO)药物,结合轻度磁脉冲序列,以提高局部皮层敏感性的磁性脑刺激的新策略,即联合磁性刺激系统(c-MSS)。小鼠左前额叶皮层中与人类DLPFC同源的脑区为PrL,磁共振成像证明SPIO可稳定存在于PrL脑区至少11天。从细胞、动物和体外模型多方面证明了c-MSS的安全性和物理性特征。建立慢性不可预测的轻度应激(CUMS)抑郁模型小鼠,使用0.1T c-MSS(每次5分钟,每天两次)进行磁干预,结果表明10 Hz磁刺激5天可快速改善CUMS小鼠的抑郁样症状,这可能与增加脑源性神经营养因子(BDNF)和改善下丘脑-垂体-肾上腺(HPA)轴有密切关系。c-MSS是一种可精准刺激小动物任意皮层靶标的新方法,这一项研究成果将极大地丰富磁刺激的潜在应用领域,促进基于磁性纳米药物的磁刺激技术临床转化。

     

    Abstract: Magnetic brain stimulation has greatly contributed to the advancement of neuroscience. However, challenges remain in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel combined magnetic stimulation system (c-MSS) was established for brain stimulation in mice. The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility. After imaging of the SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we determined their safety and physical characteristics. Depressive-like behavior was established in mice using a chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were then delivered precisely to the left PrL cortex using in situ injection. A 0.1 T magnetic field (adjustable frequency) was used for magnetic stimulation (5 min/session, two sessions daily). Biomarkers representing therapeutic effects were measured before and after c-MSS intervention. Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to SPIO nanoparticle-mediated effects. The c-MSS was safe and effective, representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals, playing a bioelectric role in neural circuit regulation, including antidepressant effects in CUMS mice. This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.

     

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