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Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits.
PLOS ONE ( IF 2.9 ) Pub Date : 2019-09-20 , DOI: 10.1371/journal.pone.0223019
Sara G Higarza 1, 2 , Silvia Arboleya 3 , Miguel Gueimonde 3 , Eneritz Gómez-Lázaro 4 , Jorge L Arias 1, 2 , Natalia Arias 1, 5
PLOS ONE ( IF 2.9 ) Pub Date : 2019-09-20 , DOI: 10.1371/journal.pone.0223019
Sara G Higarza 1, 2 , Silvia Arboleya 3 , Miguel Gueimonde 3 , Eneritz Gómez-Lázaro 4 , Jorge L Arias 1, 2 , Natalia Arias 1, 5
Affiliation
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Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH.
中文翻译：
非酒精性脂肪性肝炎的神经行为功能障碍与高氨血症、肠道菌群失调以及代谢和功能性脑区域缺陷有关。
非酒精性脂肪性肝炎（NASH）是全球最流行的疾病之一。虽然有人认为它会导致神经损伤，但其神经生理学基础仍然未知。因此，本研究的目的是通过肝脏、肠道微生物群和神经系统的相互关系来揭示 NASH 对大脑和人类行为的影响。为此，40只Sprague-Dawley大鼠被分为接受正常饮食的对照组和接受高脂肪、高胆固醇饮食的NASH组。我们的结果表明，14 周的高脂肪、高胆固醇饮食会诱发 NASH 等临床症状，包括脂肪变性和氨水平升高。NASH 组的大鼠还表现出肠道菌群失调和肠道内短链脂肪酸水平下降的证据。这可能解释了 NASH 组中观察到的认知能力缺陷，包括他们的抑郁样行为和短期记忆障碍，其部分特征是社会认知和前额叶皮层依赖性空间工作记忆的缺陷。我们还报告了这种 NASH 样病症对代谢和功能过程的影响。脑组织表现出前额皮质、丘脑、海马、杏仁核和乳头体的代谢性脑活动水平较低，同时前额皮质和小脑中的多巴胺水平降低，纹状体中的去甲肾上腺素水平降低。在本文中，我们强调氨和肠源性细菌毒素在肝肠脑神经变性中的重要作用，并讨论 NASH 中的代谢和功能性大脑区域缺陷和行为障碍。
更新日期：2019-09-21
中文翻译：
非酒精性脂肪性肝炎的神经行为功能障碍与高氨血症、肠道菌群失调以及代谢和功能性脑区域缺陷有关。
非酒精性脂肪性肝炎（NASH）是全球最流行的疾病之一。虽然有人认为它会导致神经损伤，但其神经生理学基础仍然未知。因此，本研究的目的是通过肝脏、肠道微生物群和神经系统的相互关系来揭示 NASH 对大脑和人类行为的影响。为此，40只Sprague-Dawley大鼠被分为接受正常饮食的对照组和接受高脂肪、高胆固醇饮食的NASH组。我们的结果表明，14 周的高脂肪、高胆固醇饮食会诱发 NASH 等临床症状，包括脂肪变性和氨水平升高。NASH 组的大鼠还表现出肠道菌群失调和肠道内短链脂肪酸水平下降的证据。这可能解释了 NASH 组中观察到的认知能力缺陷，包括他们的抑郁样行为和短期记忆障碍，其部分特征是社会认知和前额叶皮层依赖性空间工作记忆的缺陷。我们还报告了这种 NASH 样病症对代谢和功能过程的影响。脑组织表现出前额皮质、丘脑、海马、杏仁核和乳头体的代谢性脑活动水平较低，同时前额皮质和小脑中的多巴胺水平降低，纹状体中的去甲肾上腺素水平降低。在本文中，我们强调氨和肠源性细菌毒素在肝肠脑神经变性中的重要作用，并讨论 NASH 中的代谢和功能性大脑区域缺陷和行为障碍。
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