A mouse model of naturally occurring age-related cognitive impairment.
A mouse model of naturally occurring age-related cognitive impairment.
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DOI：
10.31491/apt.2022.09.090
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ladiges, Warren
中科院分区：
文献类型：
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作者：
Daneshjoo, Sara;Park, Joo Young;Moreno, Juliana;Rosenfeld, Manuela;Darvas, Martin;Ladiges, Warren
脑相关认知障碍（ARCI）是一种影响数百万老年人的神经系统疾病，但人们对发展更严重的神经退行性变和痴呆症的风险增加知之甚少。需要进行临床前研究以了解损伤的机制和与之相关的神经病理学。我们已经描述了C57 BL/6 J小鼠品系中自然发生的ARCI模型的特征，该模型显示出认知障碍的年龄依赖性发展。与人类一样，一些小鼠几乎没有认知障碍，而另一些小鼠则有更严重的认知障碍。因此，小鼠可被分类为抗性或易感，并且可研究两组的行为和神经病理学差异。初步观察结果显示，ARCI抗性小鼠和易感小鼠的力量和敏捷性测试评分无差异，表明ARCI易感小鼠的认知障碍不伴有日常生活活动障碍，与人类的ARCI相似。与ARCI抗性小鼠相比，ARCI易感小鼠的大脑海马区显示炎性细胞因子MCP-1增加的证据，表明炎症可能与ARCI相关。这些初步观察结果表明，C57 BL/6 J小鼠的ARCI可能是一个高影响力的模型，用于研究大脑衰老的弹性如何预测与阿尔茨海默病和其他年龄相关的神经系统疾病相关的痴呆症的弹性。
Age-related cognitive impairment (ARCI) is a neurological condition that affects millions of older people, but little is known about the increased risk of developing more severe neurodegeneration and dementia. Preclinical research is needed to understand the mechanisms of the impairment and the neuropathology associated with it. We have characterized a model of naturally occurring ARCI in the C57BL/6J mouse strain that shows an age-dependent development of cognitive impairment. As in people, some mice have little cognitive impairment while others have more severe cognitive impairment. Therefore, mice can be categorized as resistant or susceptible and the two groups can be studied for behavioral and neuropathology differences. Preliminary observations show no difference in strength and agility test scores between ARCI resistant and susceptible mice of either sex suggesting the cognitive impairment in ARCI susceptible mice is not accompanied by impairment in daily living activities, similar to ARCI in humans. The hippocampal area of the brain from ARCI susceptible mice shows evidence of an increase in the inflammatory cytokine MCP-1 compared to ARCI resistant mice, suggesting inflammation may be associated with ARCI. These preliminary observations suggest that ARCI in C57BL/6J mice could be a high-impact model to study how resilience to brain aging may predict resilience to dementia associated with Alzheimer’s disease and other age-related neurological conditions.