title: Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.
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.
authors: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Simone
authors: S
authors: Macrì
authors: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Chiara
authors: C
authors: Ceci
authors: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Martina
authors: M
authors: Proietti Onori
authors: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via G. La Masa 19, 20156 Milano, Italy.
authors: Roberto William
authors: RW
authors: Invernizzi
authors: Research Centre, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors: Erika
authors: E
authors: Bartolini
authors: Sect. Molecular and Cellular Imaging, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Luisa
authors: L
authors: Altabella
authors: Sect. Molecular and Cellular Imaging, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Rossella
authors: R
authors: Canese
authors: Sect. Respiratory and Systemic Bacterial Diseases, Dept. of Infectious, Parasitic, and Immune-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Monica
authors: M
authors: Imperi
authors: Sect. Respiratory and Systemic Bacterial Diseases, Dept. of Infectious, Parasitic, and Immune-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Graziella
authors: G
authors: Orefici
authors: Sect. Respiratory and Systemic Bacterial Diseases, Dept. of Infectious, Parasitic, and Immune-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Roberta
authors: R
authors: Creti
authors: Research Centre, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors: Immaculada
authors: I
authors: Margarit
authors: Sect. Demyelinating and Inflammatory Diseases of the CNS, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Roberta
authors: R
authors: Magliozzi
authors: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.
authors: Giovanni
authors: G
authors: Laviola
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004027:Diencephalon / Q000276:immunology* / Q000382:microbiology; D020233:Gait Disorders, Neurologic / Q000276:immunology / Q000382:microbiology*; D007794:Lameness, Animal / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D019956:Stereotypic Movement Disorder / Q000276:immunology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000276:immunology*; D013297:Streptococcus pyogenes