Tyszkiewicz Cheryl, Pardo Ingrid D, Ritenour Hayley N, Liu Chang-Ning, Somps Chris
Comparative Medicine, Worldwide Research, Development and Medical, Pfizer Inc, MS 8274-1359, PGRD, Eastern Point Road, Groton, CT, 06340, USA.
Global Pathology and Investigative Toxicology, Pfizer Inc, Groton, CT, 06340, USA.
Lab Anim Res. 2021 Aug 28;37(1):24. doi: 10.1186/s42826-021-00100-5.
CBA/J mice are standard experimental animals in auditory studies, and age-related changes in auditory pathways are well documented. However, changes in locomotion-related brain regions have not been systematically explored.
We showed an increase in immunoreactivity for glial fibrillary acidic protein (GFAP) in the cerebellar molecular layer associated with Purkinje cells in mice at 24 weeks of age but not in the younger mice. Increased GFAP immunoreactivity appeared in the form of clusters and distributed multifocally consistent with hyperplasia of astrocytes that were occasionally associated with Purkinje cell degeneration. Three out of 12 animals at 16 and 24 weeks of age exhibited pre-convulsive clinical signs. Two of these 3 animals also showed increased GFAP immunoreactivity in the cerebellum. Rotarod behavioral assessments indicated decreased performance at 24 weeks of age.
These results suggest minimal to mild reactive astrocytosis likely associated with Purkinje cell degeneration in the cerebellum at 24 weeks of age in CBA/J mice. These findings should be taken into consideration prior to using this mouse strain for studying neuroinflammation or aging.
CBA/J小鼠是听觉研究中的标准实验动物，听觉通路中与年龄相关的变化已有充分记录。然而，与运动相关的脑区变化尚未得到系统研究。
我们发现，24周龄小鼠小脑分子层中与浦肯野细胞相关的胶质纤维酸性蛋白（GFAP）免疫反应性增加，而较年轻的小鼠则未出现这种情况。GFAP免疫反应性增加表现为簇状，多灶性分布，与星形胶质细胞增生一致，偶尔与浦肯野细胞变性有关。16周龄和24周龄的12只动物中有3只出现惊厥前临床症状。这3只动物中的2只在小脑中也表现出GFAP免疫反应性增加。转棒行为评估表明，24周龄时小鼠的表现下降。
这些结果表明，CBA/J小鼠在24周龄时，小脑可能出现与浦肯野细胞变性相关的轻度至中度反应性星形胶质细胞增生。在使用该小鼠品系研究神经炎症或衰老之前，应考虑这些发现。
