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Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits


Autoři: Sara G. Higarza aff001;  Silvia Arboleya aff003;  Miguel Gueimonde aff003;  Eneritz Gómez-Lázaro aff004;  Jorge L. Arias aff001;  Natalia Arias aff001
Působiště autorů: Institute of Neurosciences of the Principality of Asturias (INEUROPA), Asturias, Spain aff001;  Laboratory of Neuroscience, Department of Psychology, University of Oviedo, Oviedo, Asturias, Spain aff002;  Department of Microbiology and Biochemistry of Dairy Products, Institute of Dairy Products of the Principality of Asturias (IPLA-CSIC), Asturias, Spain aff003;  Department of Basic Psychological Processes and their Development, Basque Country University, San Sebastián, Basque Country, Spain aff004;  Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England, United Kingdom aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0223019

Souhrn

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.

Klíčová slova:

Biology and life sciences – Biochemistry – Neuroscience – Cognitive science – Learning and memory – Psychology – Social sciences – Anatomy – Medicine and health sciences – Nutrition – Lipids – Gastroenterology and hepatology – Liver diseases – Diet – Neurology – Cognitive neurology – Cognitive impairment – Cognitive neuroscience – Cholesterol – Behavior – Brain – Prefrontal cortex – Cognition – Memory – Working memory – Fatty liver


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