在认知和情绪情感所必需的回路中,阿尔茨海默氏症样病变与神经炎症、年轻成年 TgF344-AD 大鼠的认知和动机缺陷有关。

IF 3.7 Q2 IMMUNOLOGY Brain, behavior, & immunity - health Pub Date : 2024-06-06 DOI:10.1016/j.bbih.2024.100798
Caesar M. Hernandez , Macy A. McCuiston , Kristian Davis , Yolanda Halls , Juan Pablo Carcamo Dal Zotto , Nateka L. Jackson , Lynn E. Dobrunz , Peter H. King , Lori L. McMahon
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引用次数: 0

摘要

除了细胞外的淀粉样蛋白斑块、细胞内的神经纤维tau缠结和炎症外,认知和情绪情感障碍也是阿尔茨海默病(AD)的特征。阿尔茨海默病损害的认知和情绪领域包括几种形式的决策(如时际选择)、动机减弱(冷漠增加)和执行功能受损(如工作记忆和认知灵活性)。然而,在注意力缺失症的前驱阶段,这些思维领域与支持它们的神经生物学底物之间的相互作用,或这些相互作用是否能预测注意力缺失症的严重程度(个体差异),目前仍不清楚。在这项研究中,我们对转基因费舍尔-344 AD(TgF344-AD;TgAD)大鼠进行了一系列认知和情绪测试。我们还评估了内侧前额叶皮层(mPFC)的前边缘皮层(PrL)、杏仁基底外侧(BLA)或伏隔核(NAc)(所有这些结构都直接支持上述行为)中的炎症或类似 AD 的病理标记物是否可预测行为缺陷。我们发现,TgAD 大鼠表现出不适应性决策、更大的冷漠和工作记忆受损,即使在幼年时期,相关大脑结构中的类似 AD 的病理变化也确实可以预测这些症状。此外,我们还报告说,BLA 是炎症的早期中心,值得注意的是,PrL、BLA 和 NAc 中的 AD 类病理变化可预测 BLA 炎症。这些结果表明,基于操作的电池测试可能具有足够的灵敏度来确定AD早期阶段的病理轨迹,包括神经炎症。
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In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5–7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.

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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
自引率
0.00%
发文量
0
审稿时长
97 days
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