Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Sci Rep. 2017 Mar 23;7(1):379. doi: 10.1038/s41598-017-00381-8.
Transgenic Huntington's disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Progressive developmental white matter alterations in HD monkeys were widespread and were observed not only in fiber bundles connecting cortical areas to the striatum (e.g. striatal bundle and external capsule), but also in long association fiber pathways, commissural fibers, and subcortical fiber bundle. In all fiber tracts, the data indicate an arrest in white matter development around 23 months followed by slight decline until adulthood in HD monkeys. The microstructural changes parallel the progressive motor, memory and cognitive decline previously reported as HD monkeys aged. The findings revealed the widespread progressive temporal-spatial microstructural changes in HD monkey brains from infancy to adulthood, suggesting differentiated degenerations across different brain areas during brain development.
转人类亨廷顿病猴（HD 猴）模型为研究疾病进展提供了极好的机会，这可能为开发生物标志物、早期干预和新疗法提供新的见解。使用弥散张量成像（DTI）和基于束的空间统计学（TBSS），从 6 个月到 48 个月对 HD 猴的全脑白质完整性进行了纵向检查。HD 猴的进行性发育性白质改变广泛存在，不仅在连接皮质区与纹状体的纤维束（如纹状体束和外囊）中观察到，而且在长联络纤维通路、连合纤维和皮质下纤维束中也观察到。在所有纤维束中，数据表明，在 HD 猴中，大约在 23 个月左右，白质发育停滞，随后在成年期略有下降。微观结构的变化与之前报道的 HD 猴随着年龄增长而出现的进行性运动、记忆和认知下降相平行。这些发现揭示了 HD 猴从婴儿期到成年期大脑中广泛的进行性时空微观结构变化，表明在大脑发育过程中不同脑区存在不同的退行性变。
