Cerebral Protein Synthesis as a Measure of Degenerative Changes in a Transgenic Rat Model of Alzheimer's Disease

在2020年资助期间，我们用L-1-C-14亮氨酸放射自显影方法分析了6、12和20月龄WT和TgF344-AD的雄性和雌性队列中RCP的研究。感兴趣的区域包括对背侧海马体和皮质的几个区域的详细分析。RCPS研究的结果将在目前正在准备的手稿中报告。在另一系列动物中，我们评估了突变对行为的影响。我们通过开场行为测量活动，通过T迷宫测量记忆，通过埋藏食物任务测量嗅觉，以及休息-活动节律。在两种性别中，我们证实了开放领域中淀粉样β蛋白的年龄依赖积累，女性，而不是男性，TgF344-AD大鼠在6个月和12个月龄时活动不足，但在18个月龄时，这两种基因型的活动反应水平相似。雄性和雌性TgF344-AD大鼠在学习和记忆任务中的表现都存在缺陷。雄性TgF344-AD大鼠，而不是雌性大鼠，无论年龄大小，都有性欲低下的证据。在所有大鼠中，静息-活动节律遵循典型的活动/非活动阶段，而不受基因或年龄的影响。在雄性中，家笼活动在年龄和基因上是相似的；在雌性中，无论是哪种基因，动物随着年龄的增长都不那么活跃。这些变化突出了老鼠模型中疾病的一些行为标志。疾病的早期标记物在早期诊断和治疗后的疗效评估中可能很重要。完成了对行为研究的分析，并在《神经科学前沿》上发表了报告结果的手稿。

During the 2020 funding period, we analyzed studies of rCPS with the autoradiographic L-1-C-14leucine method in cohorts of male and female WT and TgF344-AD at 6, 12, and 20 months of age. Regions of interest include a detailed analysis of the dorsal hippocampus and several regions of cortex. Results of rCPS studies will be reported in a manuscript currently in preparation. In a separate series of animals, we assessed effects of the mutations on behavior. We measured activity by means of open field behavior, memory by means of the T-maze, olfaction by means of the buried food task, and rest-activity rhythms. In both sexes, we confirmed an age-dependent buildup of amyloid-beta In the open field, female, but not male, TgF344-AD rats were hypoactive at 6 and 12 months of age but at 18 months the two genotypes were similar in levels of activity response. Both male and female TgF344-AD rats had a deficit in performance on a learning and memory task. Male TgF344-AD, but not female, rats had evidence of hyposmia regardless of age. Rest-activity rhythms followed the typical active/inactive phase in all rats regardless of genotype or age. In males, home cage activity was similar across age and genotype; in females, regardless of genotype animals were less active as they aged. These changes highlight some behavioral markers of disease in the rat model. Early markers of disease may be important in early diagnosis and assessment of efficacy when treatment becomes available. The analyses of behavioral studies are completed and a manuscript reporting results is published in Frontiers in Neuroscience.