[Brain magnetic 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].

: Magnetic brain stimulation has contributed to the advancement of neuroscience. However, there remain challenges in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel strategy for magnetic brain stimulation in mice was established using a mild magnetic pulsed sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility, namely a combined magnetic stimulation system (c-MSS). After imaging SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we were able to determine their safety and physical characteristics. Depressive-like behavior was established in mice using chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were delivered precisely to the left PrL cortex using in situ injection. A 0.1T 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. The c-MMS was found to rapidly improve depressive-like symptoms in CUMS mice after stimulation with a 10Hz field for 5 days, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to the SPIO nanoparticles mediated effect. c-MSS was shown to be 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 for CUMS mice. This expands potential applications of magnetic stimulation and progresses brain research towards clinical application.