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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doaj-878281ab46cc42729fa8d156fdf73f5c2020-12-14T00:01:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-01219483948310.3390/ijms21249483Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c MiceJacqueline V. Lara-Espinosa0Ricardo A. Santana-Martínez1Perla D. Maldonado2Mario Zetter3Enrique Becerril-Villanueva4Gilberto Pérez-Sánchez5Lenin Pavón6Dulce Mata-Espinosa7Jorge Barrios-Payán8Manuel O. López-Torres9Brenda Marquina-Castillo10Rogelio Hernández-Pando11Sección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoLaboratorio de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, CDMX 04510, MexicoLaboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, CDMX 14269, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoDepartamento de Psicoinmunologia, Instituto Nacional de Psiquiatria Ramón de la Fuente, CDMX 14370, MexicoDepartamento de Psicoinmunologia, Instituto Nacional de Psiquiatria Ramón de la Fuente, CDMX 14370, MexicoDepartamento de Psicoinmunologia, Instituto Nacional de Psiquiatria Ramón de la Fuente, CDMX 14370, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoSección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX 14080, MexicoTuberculosis (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.https://www.mdpi.com/1422-0067/21/24/9483<i>Mycobacterium tuberculosis</i>neuroinflammationbehaviour abnormalities |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jacqueline V. Lara-Espinosa Ricardo A. Santana-Martínez Perla D. Maldonado Mario Zetter Enrique Becerril-Villanueva Gilberto Pérez-Sánchez Lenin Pavón Dulce Mata-Espinosa Jorge Barrios-Payán Manuel O. López-Torres Brenda Marquina-Castillo Rogelio Hernández-Pando |
spellingShingle |
Jacqueline V. Lara-Espinosa Ricardo A. Santana-Martínez Perla D. Maldonado Mario Zetter Enrique Becerril-Villanueva Gilberto Pérez-Sánchez Lenin Pavón Dulce Mata-Espinosa Jorge Barrios-Payán Manuel O. López-Torres Brenda Marquina-Castillo Rogelio Hernández-Pando Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice International Journal of Molecular Sciences <i>Mycobacterium tuberculosis</i> neuroinflammation behaviour abnormalities |
author_facet |
Jacqueline V. Lara-Espinosa Ricardo A. Santana-Martínez Perla D. Maldonado Mario Zetter Enrique Becerril-Villanueva Gilberto Pérez-Sánchez Lenin Pavón Dulce Mata-Espinosa Jorge Barrios-Payán Manuel O. López-Torres Brenda Marquina-Castillo Rogelio Hernández-Pando |
author_sort |
Jacqueline V. Lara-Espinosa |
title |
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_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_sort |
experimental pulmonary tuberculosis in the absence of detectable brain infection induces neuroinflammation and behavioural abnormalities in male balb/c mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-12-01 |
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. |
topic |
<i>Mycobacterium tuberculosis</i> neuroinflammation behaviour abnormalities |
url |
https://www.mdpi.com/1422-0067/21/24/9483 |
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