我们报告了具有两个不同大小分支的分支轴突中线粒体运输的计算研究。为了比较,我们还研究了具有对称分支的轴突和直(无分支)轴突中的线粒体运输。了解分支轴突中线粒体运输的兴趣是由多巴胺能神经元的大尺寸乔伯激发的,死于帕金森病。由于位于各个轴突分支中的多个需求位点的能量供应失败可能是这些神经元死亡的可能原因,我们有兴趣研究分支如何影响线粒体运输。除了调查需求位点和线粒体浓度之间的线粒体通量,我们还研究了线粒体的平均年龄和线粒体的年龄密度如何取决于与soma的距离。我们确定,如果轴突分裂成两个长度不相等的分支,线粒体的平均年龄和需求位点的年龄密度分布受线粒体通量在分支连接处分裂的方式影响(线粒体的哪一部分进入较短的分支,哪一部分进入较长的分支)。然而,如果轴突分裂成两个长度相等的分支,线粒体的平均年龄和年龄密度与线粒体通量在分支连接处的分裂方式无关。这甚至适用于所有线粒体进入一个分支的情况,相当于一个直轴突。因为线粒体膜电位(许多研究人员将其视为线粒体健康的代表)随着线粒体年龄的增长而降低,线粒体年龄对轴突是对称分支还是直的(提供两个轴突的长度相同)的独立性,以及线粒体通量如何在分支连接处分裂,这可能解释了多巴胺能神经元如何维持非常大的乔木,并且仍然维持分支四肢的线粒体健康。
We report a computational
study of mitochondria transport in a branched axon with two branches of different sizes. For comparison, we also investigate mitochondria transport in an axon with symmetric branches and in a straight (unbranched) axon. The interest in understanding mitochondria transport in branched axons is motivated by the large size of arbors of dopaminergic neurons, which die in Parkinson\'s disease. Since the failure of energy supply of multiple demand sites located in various axonal branches may be a possible reason for the death of these neurons, we were interested in investigating how branching affects mitochondria transport. Besides investigating mitochondria fluxes between the demand sites and mitochondria concentrations, we also studied how the mean age of mitochondria and mitochondria age densities depend on the distance from the soma. We established that if the axon splits into two branches of unequal length, the mean ages of mitochondria and age density distributions in the demand sites are affected by how the mitochondria flux splits at the branching junction (what portion of mitochondria enter the shorter branch and what portion enter the longer branch). However, if the axon splits into two branches of equal length, the mean ages and age densities of mitochondria are independent of how the mitochondria flux splits at the branching junction. This even holds for the case when all mitochondria enter one branch, which is equivalent to a straight axon. Because the mitochondrial membrane potential (which many researchers view as a proxy for mitochondrial health) decreases with mitochondria age, the independence of mitochondria age on whether the axon is symmetrically branched or straight (providing the two axons are of the same length), and on how the mitochondria flux splits at the branching junction, may explain how dopaminergic neurons can sustain very large arbors and still maintain mitochondrial health across branch extremities.