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Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet

Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this stud...

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Autores principales: Custodio, Raly James Perez, Hobloss, Zaynab, Myllys, Maiju, Hassan, Reham, González, Daniela, Reinders, Jörg, Bornhorst, Julia, Weishaupt, Ann-Kathrin, Seddek, Abdel-latif, Abbas, Tahany, Friebel, Adrian, Hoehme, Stefan, Getzmann, Stephan, Hengstler, Jan G., van Thriel, Christoph, Ghallab, Ahmed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529844/
https://www.ncbi.nlm.nih.gov/pubmed/37759553
http://dx.doi.org/10.3390/cells12182331
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author Custodio, Raly James Perez
Hobloss, Zaynab
Myllys, Maiju
Hassan, Reham
González, Daniela
Reinders, Jörg
Bornhorst, Julia
Weishaupt, Ann-Kathrin
Seddek, Abdel-latif
Abbas, Tahany
Friebel, Adrian
Hoehme, Stefan
Getzmann, Stephan
Hengstler, Jan G.
van Thriel, Christoph
Ghallab, Ahmed
author_facet Custodio, Raly James Perez
Hobloss, Zaynab
Myllys, Maiju
Hassan, Reham
González, Daniela
Reinders, Jörg
Bornhorst, Julia
Weishaupt, Ann-Kathrin
Seddek, Abdel-latif
Abbas, Tahany
Friebel, Adrian
Hoehme, Stefan
Getzmann, Stephan
Hengstler, Jan G.
van Thriel, Christoph
Ghallab, Ahmed
author_sort Custodio, Raly James Perez
collection PubMed
description Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this study aims to unravel the effect of MASLD on brain histology, cognitive functions, and neurotransmitters. For this purpose, mice fed for 48 weeks on standard (SD) or Western diet (WD) were evaluated by behavioral tests, followed by sacrifice and analysis of the liver-brain axis including histopathology, immunohistochemistry, and biochemical analyses. Histological analysis of the liver showed features of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the WD-fed mice including lipid droplet accumulation, inflammation, and fibrosis. This was accompanied by an elevation of transaminase and alkaline phosphatase activities, increase in inflammatory cytokine and bile acid concentrations, as well as altered amino acid concentrations in the blood. Interestingly, compromised blood capillary morphology coupled with astrogliosis and microgliosis were observed in brain hippocampus of the WD mice, indicating neuroinflammation or a disrupted neurovascular unit. Moreover, attention was impaired in WD-fed mice along with the observations of impaired motor activity and balance, enhanced anxiety, and stereotyped head-twitch response (HTR) behaviors. Analysis of neurotransmitters and modulators including dopamine, serotonin, GABA, glutamate, and acetylcholine showed region-specific dysregulation in the brain of the WD-fed mice. In conclusion, the induction of MASH in mice is accompanied by the alteration of cellular morphology and neurotransmitter expression in the brain, associated with compromised cognitive functions.
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spelling pubmed-105298442023-09-28 Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet Custodio, Raly James Perez Hobloss, Zaynab Myllys, Maiju Hassan, Reham González, Daniela Reinders, Jörg Bornhorst, Julia Weishaupt, Ann-Kathrin Seddek, Abdel-latif Abbas, Tahany Friebel, Adrian Hoehme, Stefan Getzmann, Stephan Hengstler, Jan G. van Thriel, Christoph Ghallab, Ahmed Cells Article Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this study aims to unravel the effect of MASLD on brain histology, cognitive functions, and neurotransmitters. For this purpose, mice fed for 48 weeks on standard (SD) or Western diet (WD) were evaluated by behavioral tests, followed by sacrifice and analysis of the liver-brain axis including histopathology, immunohistochemistry, and biochemical analyses. Histological analysis of the liver showed features of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the WD-fed mice including lipid droplet accumulation, inflammation, and fibrosis. This was accompanied by an elevation of transaminase and alkaline phosphatase activities, increase in inflammatory cytokine and bile acid concentrations, as well as altered amino acid concentrations in the blood. Interestingly, compromised blood capillary morphology coupled with astrogliosis and microgliosis were observed in brain hippocampus of the WD mice, indicating neuroinflammation or a disrupted neurovascular unit. Moreover, attention was impaired in WD-fed mice along with the observations of impaired motor activity and balance, enhanced anxiety, and stereotyped head-twitch response (HTR) behaviors. Analysis of neurotransmitters and modulators including dopamine, serotonin, GABA, glutamate, and acetylcholine showed region-specific dysregulation in the brain of the WD-fed mice. In conclusion, the induction of MASH in mice is accompanied by the alteration of cellular morphology and neurotransmitter expression in the brain, associated with compromised cognitive functions. MDPI 2023-09-21 /pmc/articles/PMC10529844/ /pubmed/37759553 http://dx.doi.org/10.3390/cells12182331 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Custodio, Raly James Perez
Hobloss, Zaynab
Myllys, Maiju
Hassan, Reham
González, Daniela
Reinders, Jörg
Bornhorst, Julia
Weishaupt, Ann-Kathrin
Seddek, Abdel-latif
Abbas, Tahany
Friebel, Adrian
Hoehme, Stefan
Getzmann, Stephan
Hengstler, Jan G.
van Thriel, Christoph
Ghallab, Ahmed
Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title_full Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title_fullStr Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title_full_unstemmed Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title_short Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet
title_sort cognitive functions, neurotransmitter alterations, and hippocampal microstructural changes in mice caused by feeding on western diet
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529844/
https://www.ncbi.nlm.nih.gov/pubmed/37759553
http://dx.doi.org/10.3390/cells12182331
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