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恒河猴大脑白质变化的寿命轨迹。

Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

机构信息

Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Cereb Cortex. 2019 Apr 1;29(4):1584-1593. doi: 10.1093/cercor/bhy056.

Abstract

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field. Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

摘要

神经发育脑研究的进展是通过使用动物模型实现的。这些模型不仅有助于理解控制大脑发育、成熟和衰老的生物学变化,而且对于确定神经发育和与年龄相关的慢性疾病的可能机制以及评估可能与人类疾病相关的潜在干预措施也是必不可少的。恒河猴与人类的遗传关系使这些动物成为此类模型的理想候选者。它们的典型寿命为 25 年,经历了与人类相似的认知成熟和衰老。定量结构神经影像学已被提议作为追踪白质大脑成熟和衰老的候选体内生物标志物之一。虽然已经在人类中绘制了白质变化的寿命轨迹,但对于非人类灵长类动物来说,这种知识尚不可用。在这里,我们使用活体扩散成像对 44 只恒河猴样本进行分析并建立了白质微观结构寿命轨迹模型。我们报告了 8 条单独白质束的寿命轨迹的定量参数(包括斜率和峰值)。我们展示了与白质成熟和衰老相关的细胞内和细胞外微观结构成像成分的不同轨迹,并讨论了人类和恒河猴之间的相似之处和不同之处、我们研究结果的重要性以及该领域的未来方向。 意义声明:定量结构神经影像学已被提议作为追踪大脑成熟和衰老的候选体内生物标志物之一。虽然已经在人类中绘制了结构白质变化的寿命轨迹,但对于恒河猴来说,这种知识尚不可用。我们在此介绍了使用活体扩散成像对 44 只恒河猴(年龄 4-27 岁)样本的白质微观结构寿命轨迹进行分析和建模的结果。我们报告并在解剖学上绘制了与细胞内和细胞外微观结构成分相关的与白质成熟和衰老相关的寿命变化,这些成分与白质成熟和衰老有关。

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