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，我们用放射自显影l -1- c -14亮氨酸方法分析了6、12和20月龄的男性和女性WT和TgF344-AD的rCPS研究。感兴趣的区域包括对海马背侧和几个皮质区域的详细分析。rCPS研究的结果将在目前正在准备的手稿中报告。在一个单独的动物系列中，我们评估了突变对行为的影响。我们通过开放领域行为来测量活动，通过t迷宫来测量记忆，通过埋藏食物任务来测量嗅觉，以及休息-活动节律。在雄性和雌性TgF344-AD大鼠中，我们证实了β淀粉样蛋白的年龄依赖性积累。在野外，雌性而非雄性TgF344-AD大鼠在6个月和12个月时活性低下，但在18个月时，两种基因型的活性反应水平相似。雄性和雌性TgF344-AD大鼠在学习和记忆任务中的表现都有缺陷。无论年龄大小，雄性TgF344-AD大鼠均有低氧现象，而雌性大鼠无此现象。无论基因型或年龄，所有大鼠的休息-活动节律都遵循典型的活跃/不活跃阶段。在雄性中，不同年龄和基因型的家庭笼活动相似；在雌性动物中，无论基因型如何，随着年龄的增长，它们的活跃程度都有所降低。这些变化突出了大鼠模型中疾病的一些行为标记。疾病的早期标记对于早期诊断和在治疗可行时评估疗效可能很重要。行为研究的分析已经完成，报告结果的手稿发表在神经科学前沿。

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.