Zhang Xiaohan, Liu Shenquan, Zhan Feibiao, Wang Jing, Jiang Xiaofang
Department of Mathematics, South China University of Technology, Guangzhou, China.
Department of Mathematics and Science, Henan Institute of Science and Technology, Xinxiang, China.
Front Comput Neurosci. 2017 Oct 26;11:91. doi: 10.3389/fncom.2017.00091. eCollection 2017.
The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation. Through the introduction of error index (EI), which was used to measure the attenuation of the signal, we explored the amount of dendritic spine loss and dendritic trees degradation required to restore the normal regulatory function of the network, and found that there were two ranges of dendritic spine loss that could reduce EI to normal levels in the case of dopamine at a certain level, this was also true for dendritic trees. However, although these effects were the same, the mechanisms of these two cases were significant difference. Using the method of phase diagram analysis, we gained insight into the mechanism of signal degradation. Furthermore, we explored the role of cortex in MSN morphology changes dopamine depletion-induced and found that proper adjustments to cortical activity do stop the loss in dendritic spines induced by dopamine depleted. These results suggested that modifying cortical drive onto MSN might provide a new idea on clinical therapeutic strategies for Parkinson's disease.
支配纹状体的多巴胺能神经元损伤被认为是帕金森病（PD）的直接原因。在多巴胺去神经支配状态下，树突棘的丧失和树突长度的减少可能会阻止中等棘状神经元（MSN）接收来自皮层的过多兴奋性刺激，从而减轻帕金森病的症状。然而，不同实验得到的树突棘密度降低情况存在显著差异。我们开发了一种基于生物学的网络计算模型，以量化树突棘丧失和树突树退化对基底神经节（BG）信号调节的影响。通过引入用于测量信号衰减的误差指数（EI），我们探索了恢复网络正常调节功能所需的树突棘丧失量和树突树退化量，发现在多巴胺处于一定水平的情况下，存在两个树突棘丧失范围可将EI降低至正常水平，树突树情况也是如此。然而，尽管这些效应相同，但这两种情况的机制存在显著差异。使用相图分析方法，我们深入了解了信号降解的机制。此外，我们探索了皮层在多巴胺耗竭诱导的MSN形态变化中的作用，发现适当调整皮层活动确实可以阻止多巴胺耗竭诱导的树突棘丧失。这些结果表明，调节皮层对MSN的驱动可能为帕金森病的临床治疗策略提供新的思路。
