Poster Z20 - Chemomagnetic Stimulation of Neural Activity and Growth Using the Neurotransmitter Capsaicin

Introduction: Neurodegenerative diseases, like Alzheimer’s and Parkinson’s disease, often result in loss of neural tissue and cell functioning. Current literature has cited capsaicin as a possible treatment to stimulate activity and growth in neurons damaged due to neurodegenerative diseases. By stimulating these neurons, the debilitating effects of the damaged neurons and the quality of life for patients suffering from these diseases may be improved. A chemomagnetic approach is used in this work to stimulate neuronal activity and growth by interrogation with the neurotransmitter capsaicin. Iron oxide magnetic nanoparticles (MNPs) coated with poly (oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) brushes are used with alternating magnetic fields (AMFs) to locally release the neurotransmitter capsaicin from the MNPs onto hippocampal neurons. The chemomagnetic local delivery of capsaicin is investigated to influence neural activity excitation, growth, and differentiation.

Materials and

Methods: Capsaicin is encapsulated inside a temperature-responsive polymer coating (POEGMA) that functionally coats the surface of magnetic nanoparticles. AMFs are used to control the local release of the neurotransmitters onto primary rat hippocampal neurons through the magnetic heating of MNPs and the temperature response of the polymer coating. Six groups are tested (neurons alone, AMFs alone, MNPs alone, Capsaicin alone, empty MNPs with AMFs, and loaded MNPs with AMFs) and analyzed to assess the chemomagnetic effects on hippocampal neurons. Cell differentiation experiments are performed using ND 7/23 cells (DRG hybrid cell line) in enhanced culture media to evaluate the impact of the local release of capsaicin on nerve differentiation and regeneration. Cell viability and reactive oxygen species assays have also been conducted to evaluate the biological impact of the chemomagnetic approach.

Results, Conclusions, and Discussions: In vitro experiments of hippocampal neuron stimulation show that the release of capsaicin from the MNPs is triggered via AMFs. The release of capsaicin can cause excitation and stimulation of hippocampal neuron activity. In vitro experiments of ND 7/23 cells have shown that the local delivery of capsaicin increases the differentiation potential of these cells into neurons. The live/dead assay and ROS tests show no increase in deceased cells when the AMFs or MNPs are added, indicating that these methods of stimulation are non-toxic to the cells.

Iron oxide MNPs were functionally coated with POEGMA brushes that encapsulated the neurotransmitter capsaicin. These particles were used to evaluate the role of capsaicin in the stimulation of damaged neurons, both with and without the use of AMFs. In vitro studies have shown that these functionally coated MNPs worked in tandem with AMFs to produce excitation of activity in hippocampal neurons. In vitro differentiation studies show that the local delivery of capsaicin has the potential to differentiate ND 7/23 cells into neurons with axonal propagations. The toxicity of the MNPs was evaluated using live/dead assays and reactive oxygen species tests, and no toxic effects were observed.

Acknowledgements (Optional): This work has been supported by the National Science Foundation Career Award #2044713.