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.
Highlights
Physical therapies have been increasingly used for the prevention and treatment of a wide range of diseases in humans (Diana et al, 2017; Polanía et al, 2018)
We hypothesized that the left PrL cortex would be stimulated magnetically every time the magnet passed over the mouse brain
The Au nanoparticles showed identical morphology and size as the superparamagnetic iron oxide (SPIO) nanoparticles but did not improve the behavior of mice. These findings indicate that the observed antidepressive effects resulting from enhanced magnetic stimulation were due to the use of SPIO nanoparticles
Summary
Physical therapies have been increasingly used for the prevention and treatment of a wide range of diseases in humans (Diana et al, 2017; Polanía et al, 2018). Repetitive transcranial magnetic stimulation (rTMS) has been used to treat neuropsychiatric disorders due to its non-invasive, convenient, and effective properties (Hauer et al, 2019; Trevizol & Blumberger, 2019). There remain technical limitations to rTMS, including poor penetrating power, lack of precision in magnetic stimulation, limited depth of stimulation, and inadequate ability to focus on target brain regions. In small animals such as rats and mice (Fang & Wang, 2018; Sun et al, 2011), even the smallest universal coil will stimulate a whole hemisphere or even the complete brain (Salvador & Miranda, 2009; Tang et al, 2016). It is a challenge to accurately identify the underlying molecular and neural circuit mechanisms within target regions (Guadagnin et al, 2016; Meng et al, 2018). There is a need to improve technology to satisfy the rapid development of brain science research
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