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

Simone Macrì, Chiara Ceci, Martina Proietti Onori, Roberto William Invernizzi, Erika Bartolini, Luisa Altabella, Rossella Canese, Monica Imperi, Graziella Orefici, Roberta Creti, Immaculada Margarit, Roberta Magliozzi, Giovanni Laviola

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Abstract

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.

Original languageEnglish
Article number13257
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Aug 25 2015

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Macrì, S., Ceci, C., Onori, M. P., Invernizzi, R. W., Bartolini, E., Altabella, L., Canese, R., Imperi, M., Orefici, G., Creti, R., Margarit, I., Magliozzi, R., & Laviola, G. (2015). Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon. Scientific Reports, 5, [13257]. https://doi.org/10.1038/srep13257