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Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e...

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Autores principales: Macrì, Simone, Ceci, Chiara, Onori, Martina Proietti, Invernizzi, Roberto William, Bartolini, Erika, Altabella, Luisa, Canese, Rossella, Imperi, Monica, Orefici, Graziella, Creti, Roberta, Margarit, Immaculada, Magliozzi, Roberta, Laviola, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548234/
https://www.ncbi.nlm.nih.gov/pubmed/26304458
http://dx.doi.org/10.1038/srep13257
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author Macrì, Simone
Ceci, Chiara
Onori, Martina Proietti
Invernizzi, Roberto William
Bartolini, Erika
Altabella, Luisa
Canese, Rossella
Imperi, Monica
Orefici, Graziella
Creti, Roberta
Margarit, Immaculada
Magliozzi, Roberta
Laviola, Giovanni
author_facet Macrì, Simone
Ceci, Chiara
Onori, Martina Proietti
Invernizzi, Roberto William
Bartolini, Erika
Altabella, Luisa
Canese, Rossella
Imperi, Monica
Orefici, Graziella
Creti, Roberta
Margarit, Immaculada
Magliozzi, Roberta
Laviola, Giovanni
author_sort Macrì, Simone
collection PubMed
description Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.
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spelling pubmed-45482342015-08-26 Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon Macrì, Simone Ceci, Chiara Onori, Martina Proietti Invernizzi, Roberto William Bartolini, Erika Altabella, Luisa Canese, Rossella Imperi, Monica Orefici, Graziella Creti, Roberta Margarit, Immaculada Magliozzi, Roberta Laviola, Giovanni Sci Rep Article Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. Nature Publishing Group 2015-08-25 /pmc/articles/PMC4548234/ /pubmed/26304458 http://dx.doi.org/10.1038/srep13257 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Macrì, Simone
Ceci, Chiara
Onori, Martina Proietti
Invernizzi, Roberto William
Bartolini, Erika
Altabella, Luisa
Canese, Rossella
Imperi, Monica
Orefici, Graziella
Creti, Roberta
Margarit, Immaculada
Magliozzi, Roberta
Laviola, Giovanni
Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title_full Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title_fullStr Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title_full_unstemmed Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title_short Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
title_sort mice repeatedly exposed to group-a β-haemolytic streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548234/
https://www.ncbi.nlm.nih.gov/pubmed/26304458
http://dx.doi.org/10.1038/srep13257
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