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，我们分析了在6、12和20个月龄的男性和女性WT和TgF 344-AD队列中采用放射自显影L-1-C-14亮氨酸方法进行的rCPS研究。感兴趣的区域包括背海马和几个皮质区域的详细分析。rCPS研究的结果将在目前正在编写的手稿中报告。在另一系列动物中，我们评估了突变对行为的影响。我们通过旷场行为、T迷宫记忆、埋藏食物任务嗅觉和休息-活动节律来测量活动。在两种性别中，我们证实了淀粉样蛋白β的年龄依赖性积累。在开放视野中，雌性TgF 344-AD大鼠在6和12个月大时活动减退，但在18个月大时，两种基因型的活动反应水平相似，但雄性TgF 344-AD大鼠没有。 雄性和雌性TgF 344-AD大鼠在学习和记忆任务中表现出缺陷。 雄性TgF 344-AD大鼠（而非雌性）具有嗅觉减退的证据，与年龄无关。 休息活动节律遵循典型的活跃/不活跃的阶段，在所有的大鼠，无论基因型或年龄。 在雄性动物中，不同年龄和基因型的笼舍活动相似;在雌性动物中，无论基因型如何，动物随着年龄的增长活动减少。这些变化突出了大鼠模型中疾病的一些行为标志物。 疾病的早期标志物在早期诊断和治疗有效性评估中可能很重要。行为研究的分析已经完成，并在Frontiers in Neuroscience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.