DiMarco Giuliana M, Harris Breanna N, Savonenko Alena V, Soto Paul L
Department of Biological Sciences, Texas Tech University, Lubbock, TX, United States.
Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ, United States.
Front Behav Neurosci. 2023 May 12;17:1151833. doi: 10.3389/fnbeh.2023.1151833. eCollection 2023.
Memory impairment in Alzheimer's disease patients is thought to be associated with the accumulation of amyloid-beta peptides and tau proteins. However, inconsistent reports of cognitive deficits in pre-clinical studies have raised questions about the link between amyloid-beta and cognitive decline. One possible explanation may be that studies reporting memory deficits often involve behavioral assessments that entail a high stress component. In contrast, in tasks without a high stress component transgenic mice do not consistently show declines in memory. The glucocorticoid cascade hypothesis of aging and the vicious cycle of stress framework suggest that stress exacerbates dementia progression by initiating a cycle of hypothalamic-pituitary-adrenal axis activation and subsequent brain deterioration. Using the APPswe/PS1dE9 mouse model of amyloidosis, we assessed whether stressor exposure prior to testing differentially impaired cognitive performance of aged male and female mice. As part of a larger study, mice performed a delayed match-to-position (DMTP) or a 3-choice serial-reaction time (3CSRT) task. Unexpectedly, these mice did not exhibit cognitive declines during aging. Therefore, at 73 and 74 weeks of age, we exposed mice to a predator odor or forced swim stressor prior to testing to determine if stress revealed cognitive deficits. We predicted stressor exposure would decrease performance accuracy more robustly in transgenic vs. non-transgenic mice. Acute stressor exposure increased accuracy in the DMTP task, but not in the 3CSRT task. Our data suggest that acute stressor exposure prior to testing does not impair cognitive performance in APPswe/PS1dE9 mice.
阿尔茨海默病患者的记忆障碍被认为与β-淀粉样肽和tau蛋白的积累有关。然而，临床前研究中关于认知缺陷的报告不一致，这引发了人们对β-淀粉样蛋白与认知衰退之间联系的质疑。一种可能的解释是，报告记忆缺陷的研究通常涉及具有高压力成分的行为评估。相比之下，在没有高压力成分的任务中，转基因小鼠的记忆并不总是出现衰退。衰老的糖皮质激素级联假说和压力恶性循环框架表明，压力通过启动下丘脑-垂体-肾上腺轴激活和随后的脑退化循环，加剧痴呆症的进展。我们使用淀粉样变性的APPswe/PS1dE9小鼠模型，评估了在测试前暴露于应激源是否会对老年雄性和雌性小鼠的认知表现产生不同程度的损害。作为一项更大规模研究的一部分，小鼠进行了延迟位置匹配（DMTP）或三选择序列反应时间（3CSRT）任务。出乎意料的是，这些小鼠在衰老过程中并未表现出认知衰退。因此，在73和74周龄时，我们在测试前让小鼠暴露于捕食者气味或强迫游泳应激源，以确定压力是否会揭示认知缺陷。我们预测，与非转基因小鼠相比，应激源暴露会更显著地降低转基因小鼠的表现准确性。急性应激源暴露提高了DMTP任务中的准确性，但在3CSRT任务中没有。我们的数据表明，测试前的急性应激源暴露不会损害APPswe/PS1dE9小鼠的认知表现。
