Intelligent Polymer Research Institute, ARC Centre of Excellence for Electromaterials Science, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW, 2519, Australia.
Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
Sci Rep. 2018 Jun 29;8(1):9855. doi: 10.1038/s41598-018-27784-5.
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.
神经突生长和突触发生缺陷已被认为是精神病的潜在发育病因。电刺激可促进神经元诱导，包括神经突生长和分支。然而，使用 3D 电极进行电刺激对神经突生长和突触发生的影响尚未得到探索。本研究探讨了 3D 电刺激对 3D 原代皮质神经元培养物的影响。3D 电刺激改善了来自野生型和 NRG1 敲除（NRG1-KO）小鼠的 3D 神经元培养物中的神经突生长。突触小体和 PSD95 的表达在 3D 电刺激下升高。有趣的是，3D 电刺激还改善了神经细胞聚集以及 PSA-NCAM 的表达。我们的发现表明，3D 电刺激系统可以挽救 3D 培养环境中神经突生长缺陷，与更传统的 2D 细胞培养相比，3D 培养环境更接近体内生物系统，包括观察细胞聚集以及上调的 PSA-NCAM 蛋白和转录本表达。这项研究为神经发育性疾病中神经突缺陷的可能诊断平台以及与电刺激联合测试治疗方案（如药物输送）的可行平台提供了一个新概念。
