Department of Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada; Centre d'Imagerie Cérébrale, Douglas Mental Health University Institute, Montreal, Quebec, Canada.
Centre d'Imagerie Cérébrale, Douglas Mental Health University Institute, Montreal, Quebec, Canada.
Neurobiol Aging. 2022 Jan;109:216-228. doi: 10.1016/j.neurobiolaging.2021.10.003. Epub 2021 Oct 16.
Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is one of the most frequently used models in aging research. Despite frequency of use, characterization of agerelated neuroanatomical change has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in vivo in a mixed-sexcohort of F344 rats. We identified the greatest vulnerability to aging within the cortex, caudoputamen, hindbrain, and internal capsule, while the influence of sex was strongest in the caudoputamen, hippocampus, nucleus accumbens, and thalamus, many of which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared.
动物模型被广泛用于研究疾病的病理生理学，并评估新干预措施的疗效，这是改善人类疾病结局的关键步骤。Fischer 344（F344）野生型大鼠是疾病转基因模型的常用实验背景品系，也是衰老研究中最常用的模型之一。尽管使用频率很高，但 F344 大鼠的年龄相关性神经解剖结构变化特征尚未进行描述。为此，我们在混合性别队列的 F344 大鼠体内进行了一项全面的纵向研究，观察了 73 个脑区的形态学变化，并在体内正常老化过程中以体素为单位进行了研究。我们发现，大脑皮层、尾壳核、后脑和内囊最容易受到衰老的影响，而性别对尾壳核、海马体、伏隔核和丘脑的影响最大，这些区域都与记忆和运动控制回路有关，这些回路经常受到衰老和神经退行性疾病的影响。这些发现为雄性和雌性 F344 大鼠与衰老相关的神经解剖结构变化提供了基线，可供转基因模型或其他背景品系的数据进行比较。
