MAGNETO-ELECTRICAL STIMULATION OF NEURONS

Introduction:: Central nervous system (CNS) modulation is a common practice in treatment and relief therapies for many neurological disorders. In previous cases, professionals have relied on the use of Deep Brain Stimulation (DBS) to reach deep brain regions via a wire electrode and power source. While producing promising results, DBS is mechanically invasive with an extensive healing process forming glia scars. Recent research looks towards noninvasive practices using nanomaterials, particularly magnetic nanoparticles and alternating magnetic fields (AMF) to provide localized stimulation to neurons. When using magneto-electric nanoparticles (MENPs), researchers have achieved significant neuronal stimulation (1), which could lead to the replacement of existing invasive DBS procedures and eventually cure neurological diseases. Here, we will investigate if the neuronal stimulation observed with MENPs and AMF is indeed a magneto-electrical effect or relies on magnetic hyperthermia.


Materials and Methods:: MENPs synthesized by collaborators in large batches were characterized for morphology by transmission electron microscopy, and for hydrodynamic size and zeta potential through dynamic light scattering. In this study, the objective aims to perform an in vitro stimulation, hence requires the use of plated primary neurons. Primary neurons were extracted from newborn Sprague Dawley rats, where cortical and hippocampal neurons were isolated and cultured. The fluorescent Ca2+ indicator Fluo-4 was utilized to monitor neural activity. MENPs and AMF of 250 kHz and 18 kA/m were used to stimulate neurons. A semi-automatic data analysis procedure was used to analyze the recorded Ca2+ imaging videos and evaluate neural stimulation. Minimum concentration MENPs for stimulation will be determined and temperature analysis will be performed.


Results, Conclusions, and Discussions:: Completing MENP stimulation presented us with the minimum concentration required for fluorescence to be 200 μg/ mL as seen in Figure 1A-B. Fluorescence analysis revealed increased neuron activity in stimulation periods shown in 1C, where neurons with AMFs and nanoparticles glowed brighter. Further, testing of nanoparticles with applied magnetic fields showed a low increase in temperature of the particles in solution in Figure 1D and therefore a minimal heating effect. Interpreting this, MENPs stimulate neurons electrically as opposed to thermally given their low temperature increase when exposed to AMFs. Preliminary data shows promising results of electrical MENP interaction applied to neuron stimulation. Results of this study can be further applied to MENP research in the creation of new therapies for healthy tissue. Future work may determine how MENPs localize on neurons where any potential toxicity can also be observed. Stimulation on additional neuron species will also be conducted to ensure methodology is effective across all neurons.

Acknowledgements (Optional): :

References (Optional): : References: (1) Kozielski, K. L., Jahanshahi, A., Gilbert, H. B., Yu, Y., Erin, Ö., Francisco, D., ... & Sitti, M. (2021). Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice. Science advances, 7(3), eabc4189.