Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital Cambridge, UK ; Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK.
EA, 2027: Laboratoire de Psychopathologie et de Neuropsychologie, Université Paris 8 St-Denis, France ; CEA, DSV, I2BM, MIRCen Fontenay-aux-Roses, France ; CNRS, URA 2210 Fontenay-aux-Roses, France.
Front Aging Neurosci. 2014 May 6;6:82. doi: 10.3389/fnagi.2014.00082. eCollection 2014.
Cerebral atrophy is one of the most widely brain alterations associated to aging. A clear relationship has been established between age-associated cognitive impairments and cerebral atrophy. The mouse lemur (Microcebus murinus) is a small primate used as a model of age-related neurodegenerative processes. It is the first non-human primate in which cerebral atrophy has been correlated with cognitive deficits. Previous studies of cerebral atrophy in this model were based on time consuming manual delineation or measurement of selected brain regions from magnetic resonance images (MRI). These measures could not be used to analyse regions that cannot be easily outlined such as the nucleus basalis of Meynert or the subiculum. In humans, morphometric assessment of structural changes with age is generally performed with automated procedures such as voxel-based morphometry (VBM). The objective of our work was to perform user-independent assessment of age-related morphological changes in the whole brain of large mouse lemur populations thanks to VBM. The study was based on the SPMMouse toolbox of SPM 8 and involved thirty mouse lemurs aged from 1.9 to 11.3 years. The automatic method revealed for the first time atrophy in regions where manual delineation is prohibitive (nucleus basalis of Meynert, subiculum, prepiriform cortex, Brodmann areas 13-16, hypothalamus, putamen, thalamus, corpus callosum). Some of these regions are described as particularly sensitive to age-associated alterations in humans. The method revealed also age-associated atrophy in cortical regions (cingulate, occipital, parietal), nucleus septalis, and the caudate. Manual measures performed in some of these regions were in good agreement with results from automatic measures. The templates generated in this study as well as the toolbox for SPM8 can be downloaded. These tools will be valuable for future evaluation of various treatments that are tested to modulate cerebral aging in lemurs.
脑萎缩是与衰老相关的最广泛的大脑改变之一。年龄相关的认知障碍与脑萎缩之间存在明确的关系。鼠狐猴（Microcebus murinus）是一种小型灵长类动物，被用作与年龄相关的神经退行性过程的模型。它是第一个与认知缺陷相关的非人类灵长类动物。以前对这种模型的脑萎缩的研究是基于磁共振成像（MRI）的手动勾画或测量选定脑区。这些措施不能用于分析那些不能轻易勾勒出的区域，如梅尼埃基底核或下托。在人类中，形态测量学评估与年龄相关的结构变化通常采用基于体素的形态测量学（VBM）等自动程序进行。我们的工作目标是通过 VBM 对大型鼠狐猴种群的整个大脑进行与年龄相关的形态变化的用户独立评估。该研究基于 SPM8 的 SPMMouse 工具箱，涉及 30 只年龄在 1.9 至 11.3 岁之间的鼠狐猴。该自动方法首次揭示了在手动勾画受限的区域（梅尼埃基底核、下托、梨状皮层、Brodmann 区域 13-16、下丘脑、壳核、丘脑、胼胝体）出现萎缩。其中一些区域被描述为对人类与年龄相关的改变特别敏感。该方法还揭示了皮质区域（扣带回、枕叶、顶叶）、隔核和尾状核与年龄相关的萎缩。在这些区域中的一些区域中进行的手动测量与自动测量的结果非常吻合。本研究中生成的模板以及用于 SPM8 的工具箱均可下载。这些工具对于未来评估各种治疗方法非常有价值，这些方法被测试用于调节灵长类动物的大脑衰老。
