Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D

Qingsheng Zhang,Gordon G Wallace,Stephen Beirne,Dorna Esrafilzadeh,Xu-Feng Huang,Kewei Shu

doi:10.1038/s41598-018-27784-5

Abstract

Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.

Highlights

Electrical stimulation has been reported to induce enhanced neurite outgrowth in 3D cell culture[6]
We described the design and fabrication of an interdigitated 3D electrode system and examined the effect of 3D electrical stimulation delivered by these electrodes on 3D primary cortical neuronal cultures from normal and disease model mice
To the best of the authors’ knowledge, this is the first report demonstrating the effect of 3D electrical stimulation on neurite outgrowth in primary neural cultures from both normal and disease models of schizophrenia

Summary

Introduction

Electrical stimulation has been reported to induce enhanced neurite outgrowth in 3D cell culture[6]. The effect of 3D electrical stimulation from 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. An interdigitated 3D electrode system has previously been developed and reported by our group[17], but its application on biological systems has not been investigated. We described the design and fabrication of an interdigitated 3D electrode system and examined the effect of 3D electrical stimulation delivered by these electrodes on 3D primary cortical neuronal cultures from normal and disease model mice. We compared the differential effect of electrical stimulation on neurite growth, synaptogenesis, and cell migration between 2D and 3D. We tried to unravel a potential molecular biological mechanism that may underlie these effects

Methods

Results

Conclusion