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. 2020 Jul 18;41(4):381-394.
doi: 10.24272/j.issn.2095-8137.2020.076.

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

Qing-Bo Lu  1 , Jian-Fei Sun  2 , Qu-Yang Yang  3 , Wen-Wen Cai  1 , Meng-Qin Xia  1 , Fang-Fang Wu  1 , Ning Gu  4 , Zhi-Jun Zhang  5
Affiliations

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

Qing-Bo Lu et al. Zool Res. .

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.

Keywords: Bioelectronics; Depression; Magnetic stimulation; SPIO nanoparticles.

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Figures

Figure 1
Figure 1. Construction of combined magnetic stimulation system (c-MSS) and microinjection of mice
Figure 2
Figure 2. MRI tracing and cytotoxicity of nanodrugs
Figure 3
Figure 3. Measurement of magneto-electric induction and physical effects in a hydrogel phantom
Figure 4
Figure 4. Simulation using COMSOL software of magnetization, induction of electric field, induction of electric current, and induction of stress field for SPIO nanoparticles in presence of a 10 Hz magnetic field
Figure 5
Figure 5. Treatment of CUMS mice and confirmation of effects of c-MSS through behavioral experiments
Figure 6
Figure 6. Comparison of biomarker levels for effective anti-depression in mice
See this image and copyright information in PMC

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Grants and funding

This work was supported by grants from National Natural Science Foundation of China (81830040 to Z.J.Z.), National Key Projects for Research and Development Program of China (2016YFC1306700 to Z.J.Z., 2017YFA0104302 to N.G., and 2017YFA0104301 to J.F.S.), and Program of Excellent Talents in Medical Science of Jiangsu Province (JCRCA2016006 to Z.J.Z.)