Synergistic nanomagnetic forces and aripiprazole potentiate guided neurite outgrowth.

Abstract

Neuronal circuits rely on particular, consistent connections, called synapses, to communicate effectively. Lack of synapses, which can result from a lack of neurite branching, and misoriented axons can lead to neuronal miscommunication, resulting in mental disorders such as schizophrenia. In previous studies, numerous methods have been identified to initiate greater neurite branching, including antipsychotic drugs such as aripiprazole and olanzapine. However, antipsychotics alone have not been shown to orient neurites. Previously, other researchers and we have demonstrated that applying nanomagnetic forces (NMF) can orient neurite outgrowth in the direction of the magnetic ascent. In this study, we examined the separate and combined effects of antipsychotic drugs and NMF on neurite growth patterns of PC12 cells. PC12s were seeded on coated Petri dishes and allowed to reach ∼10% confluence. Then we incubated 10 µg/ml starch-NH2 magnetic nanoparticles (d:iron oxide = 100 nm) for 24 h. Culture media containing 1 µM aripiprazole and 20 ng/ml NGF was added every other day. Cells were placed in one of three external magnetic fields and incubated for seven days, imaged (Leica DMi8 brightfield) at days 0, 3, 5, and 7. Extracted neurite traces had preferred neurite growth directions in each magnetic field of [1: 300°, 345°], [2: 90°, 120°], and [3: 345°, 360°], respectively. In contrast, no field conditions showed a uniform distribution of neurites across all angles [0° - 360°]. Additionally, neurites growing within the magnetic fields grew 17%, 16%, and 17% longer than neurites in the control group. These findings indicate that NMFs, in synergy with antipsychotic drugs, may help orient and guide neurites for targeted cell therapeutics and tissue engineering.