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

Autor: Sara G. Higarza, Silvia Arboleya, Miguel Gueimonde, Eneritz Gómez-Lázaro, Jorge L. Arias, Natalia Arias
Přispěvatelé: Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), Arboleya, Silvia [0000-0002-6155-5822], Gueimonde Fernández, Miguel [0000-0002-0192-901X], Arboleya, Silvia, Gueimonde Fernández, Miguel
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Social Sciences
Hippocampus
Gut flora
Biochemistry
Cholesterol
Dietary
Rats
Sprague-Dawley
Cognition
Learning and Memory
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Medicine and Health Sciences
Psychology
Hyperammonemia
Prefrontal cortex
Cognitive Impairment
Multidisciplinary
biology
Cognitive Neurology
Liver Diseases
Fatty liver
Brain
Lipids
Cholesterol
Neurology
Liver
Medicine
Anatomy
Research Article
medicine.drug
medicine.medical_specialty
Mammillary body
Science
Cognitive Neuroscience
Prefrontal Cortex
Gastroenterology and Hepatology
Diet
High-Fat
digestive system
03 medical and health sciences
Memory
Dopamine
Internal medicine
medicine
Animals
Humans
Working Memory
Nutrition
Behavior
Working memory
business.industry
Biology and Life Sciences
medicine.disease
biology.organism_classification
digestive system diseases
Diet
Gastrointestinal Microbiome
Fatty Liver
Disease Models
Animal
030104 developmental biology
Endocrinology
Cognitive Science
Dysbiosis
Steatohepatitis
Cognition Disorders
business
030217 neurology & neurosurgery
Neuroscience
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Scopus
RUO. Repositorio Institucional de la Universidad de Oviedo
PLoS ONE
PLoS ONE, Vol 14, Iss 9, p e0223019 (2019)
Popis: 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.
This work was supported by the Ministry of Science, Innovation and Universities (PSI2017-83893-R to JLA) and the Ministry of Economy and Business (PSI2015-63658-R, PSI2015-73111-EXP to JLA, and PSI2017-90806-REDT to JLA) (Spain).
Databáze: OpenAIRE
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