Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events

Worldwide, and especially in Western civilizations, most of the staple diets contain high amounts of fat and refined carbohydrates, leading to an increasing number of obese individuals. In addition to inducing metabolic disorders, energy dense food intake has been suggested to impair brain functions...

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Autores principales:	Gabriela Cristina de Paula, Henver S. Brunetta, Daiane F. Engel, Joana M. Gaspar, Licio A. Velloso, David Engblom, Jade de Oliveira, Andreza Fabro de Bem
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	high fat diet cognition neuroinflammation blood–brain barrier memory depression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/21cb614e079548e1a1e9a291bc392022
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spelling	oai:doaj.org-article:21cb614e079548e1a1e9a291bc3920222021-11-04T08:39:41ZHippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events1662-453X10.3389/fnins.2021.734158https://doaj.org/article/21cb614e079548e1a1e9a291bc3920222021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.734158/fullhttps://doaj.org/toc/1662-453XWorldwide, and especially in Western civilizations, most of the staple diets contain high amounts of fat and refined carbohydrates, leading to an increasing number of obese individuals. In addition to inducing metabolic disorders, energy dense food intake has been suggested to impair brain functions such as cognition and mood control. Here we demonstrate an impaired memory function already 3 days after the start of a high-fat diet (HFD) exposure, and depressive-like behavior, in the tail suspension test, after 5 days. These changes were followed by reduced synaptic density, changes in mitochondrial function and astrocyte activation in the hippocampus. Preceding or coinciding with the behavioral changes, we found an induction of the proinflammatory cytokines TNF-α and IL-6 and an increased permeability of the blood–brain barrier (BBB), in the hippocampus. Finally, in mice treated with a TNF-α inhibitor, the behavioral and BBB alterations caused by HFD-feeding were mitigated suggesting that inflammatory signaling was critical for the changes. In summary, our findings suggest that HFD rapidly triggers hippocampal dysfunction associated with BBB disruption and neuroinflammation, promoting a progressive breakdown of synaptic and metabolic function. In addition to elucidating the link between diet and cognitive function, our results might be relevant for the comprehension of the neurodegenerative process.Gabriela Cristina de PaulaGabriela Cristina de PaulaHenver S. BrunettaDaiane F. EngelDaiane F. EngelJoana M. GasparLicio A. VellosoDavid EngblomJade de OliveiraAndreza Fabro de BemAndreza Fabro de BemFrontiers Media S.A.articlehigh fat dietcognitionneuroinflammationblood–brain barriermemorydepressionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high fat diet cognition neuroinflammation blood–brain barrier memory depression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	high fat diet cognition neuroinflammation blood–brain barrier memory depression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Gabriela Cristina de Paula Gabriela Cristina de Paula Henver S. Brunetta Daiane F. Engel Daiane F. Engel Joana M. Gaspar Licio A. Velloso David Engblom Jade de Oliveira Andreza Fabro de Bem Andreza Fabro de Bem Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
description	Worldwide, and especially in Western civilizations, most of the staple diets contain high amounts of fat and refined carbohydrates, leading to an increasing number of obese individuals. In addition to inducing metabolic disorders, energy dense food intake has been suggested to impair brain functions such as cognition and mood control. Here we demonstrate an impaired memory function already 3 days after the start of a high-fat diet (HFD) exposure, and depressive-like behavior, in the tail suspension test, after 5 days. These changes were followed by reduced synaptic density, changes in mitochondrial function and astrocyte activation in the hippocampus. Preceding or coinciding with the behavioral changes, we found an induction of the proinflammatory cytokines TNF-α and IL-6 and an increased permeability of the blood–brain barrier (BBB), in the hippocampus. Finally, in mice treated with a TNF-α inhibitor, the behavioral and BBB alterations caused by HFD-feeding were mitigated suggesting that inflammatory signaling was critical for the changes. In summary, our findings suggest that HFD rapidly triggers hippocampal dysfunction associated with BBB disruption and neuroinflammation, promoting a progressive breakdown of synaptic and metabolic function. In addition to elucidating the link between diet and cognitive function, our results might be relevant for the comprehension of the neurodegenerative process.
format	article
author	Gabriela Cristina de Paula Gabriela Cristina de Paula Henver S. Brunetta Daiane F. Engel Daiane F. Engel Joana M. Gaspar Licio A. Velloso David Engblom Jade de Oliveira Andreza Fabro de Bem Andreza Fabro de Bem
author_facet	Gabriela Cristina de Paula Gabriela Cristina de Paula Henver S. Brunetta Daiane F. Engel Daiane F. Engel Joana M. Gaspar Licio A. Velloso David Engblom Jade de Oliveira Andreza Fabro de Bem Andreza Fabro de Bem
author_sort	Gabriela Cristina de Paula
title	Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
title_short	Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
title_full	Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
title_fullStr	Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
title_full_unstemmed	Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events
title_sort	hippocampal function is impaired by a short-term high-fat diet in mice: increased blood–brain barrier permeability and neuroinflammation as triggering events
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/21cb614e079548e1a1e9a291bc392022
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Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events

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