微生物驱动的代谢途径改变和老年雌性 TgF344-AD 大鼠认知能力受损

IF 1.7 Q3 CLINICAL NEUROLOGY Aging brain Pub Date : 2024-01-01 DOI:10.1016/j.nbas.2024.100119
Abbi R. Hernandez , Erik Parker , Maham Babar , Anisha Banerjee , Sarah Ding , Alexis Simley , Thomas W. Buford
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引用次数: 0

摘要

阿尔茨海默病(AD)不仅会影响认知和神经病理学,还会影响其他几个方面,包括肠道微生物组(GMB)组成和新陈代谢的改变,从而对生活质量产生负面影响,并可能导致机体损伤。研究人员对20+月龄的雌性TgF344-AD大鼠和野生型大鼠进行了认知测试,测试任务包括任务获取、物体识别记忆、焦虑样行为和空间导航等多个认知领域。此外,还进行了代谢表型、整个肠道(十二指肠、空肠、回肠、结肠和粪便)的 GMB 测序、神经病理学负担评估和标记基因功能丰度预测 (PICRUSt2)。TgF344-AD大鼠在多个领域表现出明显的认知障碍,以及区域特异性GMB菌群失调。利用典型对应分析(CCA)研究了外围因素之间的关系,发现 GMB 变化与认知和代谢因素之间存在相关性。此外,在 TgF344-AD 大鼠体内,有助于重要代谢途径的肠道微生物群落发生了显著变化。这些数据表明,菌群失调可能会通过改变正常脑功能所必需的代谢相关酶通路来影响注意力缺失症的认知结果。此外,这些变化主要是在碳水化合物消化所需的肠段而非粪便样本中观察到的。这些数据支持以肠道和微生物组健康为目标来治疗注意力缺失症。
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Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats

Alzheimer’s disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

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Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
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