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成年室管下神经发生的数学模型。

A mathematical model of adult subventricular neurogenesis.

机构信息

Department of Engineering Science, University of Oxford, , Parks Road, Oxford OX1 3PJ, UK.

出版信息

J R Soc Interface. 2012 Oct 7;9(75):2414-23. doi: 10.1098/rsif.2012.0193. Epub 2012 May 9.

Abstract

Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in bioluminescent imaging (BLI) allow direct in vivo imaging of neurogenesis, and in order to interpret the experimental results, mathematical models are necessary. This study proposes such a mathematical model that describes adult mammalian neurogenesis occurring in the subventricular zone and the subsequent migration of cells through the rostral migratory stream to the olfactory bulb (OB). This model assumes that a single chemoattractant is responsible for cell migration, secreted both by the OB and in an endocrine fashion by the cells involved in neurogenesis. The solutions to the system of partial differential equations are compared with the physiological rodent process, as previously documented in the literature and quantified through the use of BLI, and a parameter space is described, the corresponding solution to which matches that of the rodent model. A sensitivity analysis shows that this parameter space is stable to perturbation and furthermore that the system as a whole is sloppy. A large number of parameter sets are stochastically generated, and it is found that parameter spaces corresponding to physiologically plausible solutions generally obey constraints similar to the conditions reported in vivo. This further corroborates the model and its underlying assumptions based on the current understanding of the investigated phenomenon. Concomitantly, this leaves room for further quantitative predictions pertinent to the design of future proposed experiments.

摘要

神经发生是近年来研究的热点,许多作者都探讨了该过程的现象学、调控机制及其潜在的目的。近年来,生物发光成像(BLI)的发展使得对神经发生的直接活体成像成为可能,为了解释实验结果,需要建立数学模型。本研究提出了一个这样的数学模型,用于描述成年哺乳动物在侧脑室下区发生的神经发生,以及随后细胞通过前脑皮质流迁移到嗅球(OB)的过程。该模型假设一种单一的趋化因子负责细胞迁移,由 OB 分泌,并以内分泌的方式由参与神经发生的细胞分泌。该偏微分方程组的解与之前文献中记录的生理啮齿动物过程进行了比较,并通过 BLI 进行了量化,描述了一个参数空间,其对应的解与啮齿动物模型的解相匹配。敏感性分析表明,该参数空间对扰动具有稳定性,而且整个系统是“混乱”的。随机生成了大量的参数集,发现与生理上合理的解相对应的参数空间通常遵循类似于体内报告的条件的约束。这进一步证实了该模型及其基于对所研究现象的现有理解的假设。同时,这为未来提出的实验设计提供了进一步的定量预测的空间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0749/3427514/6e63be3ff704/rsif20120193-g1.jpg

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