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Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice

Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogen...

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Autores principales: Lara-Espinosa, Jacqueline V., Santana-Martínez, Ricardo A., Maldonado, Perla D., Zetter, Mario, Becerril-Villanueva, Enrique, Pérez-Sánchez, Gilberto, Pavón, Lenin, Mata-Espinosa, Dulce, Barrios-Payán, Jorge, López-Torres, Manuel O., Marquina-Castillo, Brenda, Hernández-Pando, Rogelio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763936/
https://www.ncbi.nlm.nih.gov/pubmed/33322180
http://dx.doi.org/10.3390/ijms21249483
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author Lara-Espinosa, Jacqueline V.
Santana-Martínez, Ricardo A.
Maldonado, Perla D.
Zetter, Mario
Becerril-Villanueva, Enrique
Pérez-Sánchez, Gilberto
Pavón, Lenin
Mata-Espinosa, Dulce
Barrios-Payán, Jorge
López-Torres, Manuel O.
Marquina-Castillo, Brenda
Hernández-Pando, Rogelio
author_facet Lara-Espinosa, Jacqueline V.
Santana-Martínez, Ricardo A.
Maldonado, Perla D.
Zetter, Mario
Becerril-Villanueva, Enrique
Pérez-Sánchez, Gilberto
Pavón, Lenin
Mata-Espinosa, Dulce
Barrios-Payán, Jorge
López-Torres, Manuel O.
Marquina-Castillo, Brenda
Hernández-Pando, Rogelio
author_sort Lara-Espinosa, Jacqueline V.
collection PubMed
description Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogenic substrate of such manifestations have remained unknown. Here, using a mouse model of progressive pulmonary TB, we report that, even in the absence of brain infection, TB is associated with marked increased synthesis of both inflammatory and anti-inflammatory cytokines in discrete brain areas such as the hypothalamus, the hippocampal formation and cerebellum accompanied by substantial changes in the synthesis of neurotransmitters. Moreover, histopathological findings of neurodegeneration and neuronal death were found as infection progressed with activation of p38, JNK and reduction in the BDNF levels. Finally, we perform behavioural analysis in infected mice throughout the infection, and our data show that the cytokine and neurochemical changes were associated with a marked onset of cognitive impairment as well as depressive- and anxiety-like behaviour. Altogether, our results suggest that besides pulmonary damage, TB is accompanied by an extensive neuroinflammatory and neurodegenerative state which explains some of the behavioural abnormalities found in TB patients.
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spelling pubmed-77639362020-12-27 Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice Lara-Espinosa, Jacqueline V. Santana-Martínez, Ricardo A. Maldonado, Perla D. Zetter, Mario Becerril-Villanueva, Enrique Pérez-Sánchez, Gilberto Pavón, Lenin Mata-Espinosa, Dulce Barrios-Payán, Jorge López-Torres, Manuel O. Marquina-Castillo, Brenda Hernández-Pando, Rogelio Int J Mol Sci Article Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogenic substrate of such manifestations have remained unknown. Here, using a mouse model of progressive pulmonary TB, we report that, even in the absence of brain infection, TB is associated with marked increased synthesis of both inflammatory and anti-inflammatory cytokines in discrete brain areas such as the hypothalamus, the hippocampal formation and cerebellum accompanied by substantial changes in the synthesis of neurotransmitters. Moreover, histopathological findings of neurodegeneration and neuronal death were found as infection progressed with activation of p38, JNK and reduction in the BDNF levels. Finally, we perform behavioural analysis in infected mice throughout the infection, and our data show that the cytokine and neurochemical changes were associated with a marked onset of cognitive impairment as well as depressive- and anxiety-like behaviour. Altogether, our results suggest that besides pulmonary damage, TB is accompanied by an extensive neuroinflammatory and neurodegenerative state which explains some of the behavioural abnormalities found in TB patients. MDPI 2020-12-13 /pmc/articles/PMC7763936/ /pubmed/33322180 http://dx.doi.org/10.3390/ijms21249483 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lara-Espinosa, Jacqueline V.
Santana-Martínez, Ricardo A.
Maldonado, Perla D.
Zetter, Mario
Becerril-Villanueva, Enrique
Pérez-Sánchez, Gilberto
Pavón, Lenin
Mata-Espinosa, Dulce
Barrios-Payán, Jorge
López-Torres, Manuel O.
Marquina-Castillo, Brenda
Hernández-Pando, Rogelio
Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title_full Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title_fullStr Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title_full_unstemmed Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title_short Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice
title_sort experimental pulmonary tuberculosis in the absence of detectable brain infection induces neuroinflammation and behavioural abnormalities in male balb/c mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763936/
https://www.ncbi.nlm.nih.gov/pubmed/33322180
http://dx.doi.org/10.3390/ijms21249483
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