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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10529844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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