Magnetoelectric nanoparticle technology for mitigating motor deficits in Parkinsonian mice

Introduction: Deep brain stimulation (DBS) technology involves wired-in powering of electrodes to modulate deep brain targets in both clinical and preclinical settings. Previously, we demonstrated the feasibility of magnetoelectric nanoparticle (MENP)-based DBS for wireless modulation of the subthalamic nucleus (STh) in mice. However, key aspects such as their ability to alleviate symptoms in disease models, long-term stability and efficacy, as well as optimal magnetic field parameters used to power the particles, remain unaddressed. Material and method: Herein, for the first time, we applied MENP-based STh-DBS in a Parkinson's disease (PD) model induced by 6-hydroxydopamine (6-OHDA) lesioning to evaluate their potential to alleviate motor deficits. Throughout a parallel study, mice were monitored longitudinally for up to 18 months post injection to assess MENPs retention, efficacy, and long-term local effects. Results: MENP-based STh-DBS using a field of 140 Hz, 220 mT direct current (DC) and 8 mT of alternating current (AC) was able to improve the locomotion of 6-OHDA treated mice with over 95 % dopaminergic cell loss in the substantia nigra. Postmortem assessment revealed no evidence of sustained or enhanced astro- or microgliosis over 18 months, and no changes in MENP retention or performance. Conclusion: MENP-based STh-DBS can counteract behavioral disturbances caused by impaired neural circuits following extensive dopaminergic cell loss in PD mice. Additionally, no adverse effects or loss of efficacy were observed over time for up to 18 months with respect to astro- and microgliosis. While effective modulation was only achieved with a higher magnetic coil configuration, this finding represents a critical step toward refining MENP-based neuromodulation in PD.