Lin Ching-Yi, Huang Whitney J, Li Kevin, Swanson Roy, Cheung Brian, Lin Vernon W, Lee Yu-Shang
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Department of Physical Medicine and Rehabilitation, Cleveland Clinic, Cleveland, OH, USA.
J Neural Eng. 2015 Apr;12(2):026013. doi: 10.1088/1741-2560/12/2/026013. Epub 2015 Mar 13.
Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function.
To test our hypotheses, we examined the effects of MS on neurite growth of neuroscreen-1 (NS-1) cells over the pulse frequencies of 1, 5 and 10 Hz at field intensities controlled via machine output (MO). Cells were treated with either 30% or 40% MO. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (∼5%) electromagnetic current density while the remaining area (zone 2) received maximal (∼95%) current density. Plated NS-1 cells were exposed to MS twice per day for three days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF).
We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in bolstering longest neurite outgrowth, best seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells.
These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating its use into potential therapeutic strategies.
磁刺激(MS)是一种治疗神经精神疾病的潜在方法。本研究调查MS调节的神经元活动是否能转化为神经元分支的特定变化,从而调节突触活动和功能。
为了验证我们的假设,我们在通过机器输出(MO)控制的场强下,研究了1、5和10Hz脉冲频率的MS对神经筛选-1(NS-1)细胞神经突生长的影响。细胞分别用30%或40%的MO处理。由于圆形MS线圈的特性,网格化盖玻片的中心区域(区域1)接收的电磁电流密度最小(约5%),而其余区域(区域2)接收的电流密度最大(约95%)。接种的NS-1细胞每天接受两次MS处理,持续三天,然后评估神经突的长度和数量以及脑源性神经营养因子(BDNF)的表达。
我们发现,MS显著影响最长神经突(轴突样)的生长,但对较短神经突(树突样)的生长没有显著影响。此外,MS诱导的最长神经突生长变化在区域1最为明显,而在区域2则不明显。MS的作用具有强度依赖性,在促进最长神经突生长方面最为明显,在10Hz MS组中最为显著。此外,我们发现MS增加的BDNF表达和分泌也具有频率依赖性。综上所述,我们的结果表明,当不同频率和强度应用于NS-1细胞的神经突部分(最长神经突与较短树突)时,MS会产生不同的作用。
这些发现支持了MS增加BDNF表达和信号传导的概念,BDNF塑造了最长神经突的分支和连接,从而调节神经元活动。了解MS的潜在机制对于将其有效应用于潜在治疗策略至关重要。