In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense-core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the ‘dying back’ pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.

中文翻译：

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密集核心囊泡存在于过境布顿中的年龄：模拟轴突乔木中密集核心囊泡的平均年龄，考虑常驻和过境囊泡种群

在神经元中，神经肽在胞体中合成，然后在密集核囊泡 (DCV) 中沿轴突运输。DCV 在位于轴突末端的静脉曲张中被捕获，称为 en passant boutons，它们是积累和释放神经递质的活跃末端部位。最近开发的实验技术允许估计轴突末端不同位置的 DCV 的年龄。准确模拟 boutons 中 DCV 的平均年龄需要开发一个模型，该模型将解释常驻、过境顺行和过境逆行 DCV 人口。在本文中，开发了这样的模型。该模型应用于模拟果蝇 II 型运动神经元中的 DCV 传输。该模型模拟轴突终端中的 DCV 传输和捕获，并可以预测 en passant boutons 中 DCV 的年龄密度分布以及 boutons 中的 DCV 平均年龄。远端 boutons 中旧细胞器的预测流行可能解释了在帕金森病的多巴胺能神经元中观察到的轴突变性的“消退”模式。居住在远端 boutons 的较旧 DCV 的年龄与居住在近端 boutons 的较年轻 DCV 的年龄之间的两小时预测差异与从实验观察得出的年龄差异的近似估计一致。发现常驻 DCV 的年龄密度是双峰的，这是因为 DCV 是从两个过渡状态捕获的：