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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.

Macrì S, Ceci C, Onori MP, Invernizzi RW, Bartolini E, Altabella L, Canese R, Imperi M, Orefici G, Creti R, Margarit I, Magliozzi R, Laviola G - Sci Rep (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Rearing behavior in the elevated 0-maze (week 11, boost 2).The graph shows the duration of rearing behavior (s) in the elevated 0-maze during a 5-minutes long test session performed after the second boost (week 11). GAS mice significantly differ from CTRL mice. *p < 0.05. N = 10 per group.
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f4: Rearing behavior in the elevated 0-maze (week 11, boost 2).The graph shows the duration of rearing behavior (s) in the elevated 0-maze during a 5-minutes long test session performed after the second boost (week 11). GAS mice significantly differ from CTRL mice. *p < 0.05. N = 10 per group.

Mentions: We evaluated the behavioral profile of naïve subjects on the E0M test after both the first injection (week 5) and the second boost (week 11). Average values and standard errors of all observed data are reported in the supplementary material (see Table 1SM). As expected, experimental subjects showed a remarkable preference for the closed than the open sectors of the maze, whereby they spent approximately 85% of their time in the former and 15% in the latter. Following the first injection, CTRL and GAS mice did not show significant differences in general locomotion (frequency of entries, treatment: F(1,18) = 0.01, p = 0.93), time spent in the open arms (treatment: F(1,18) = 0.01, p = 0.91), and the ethological measures considered (duration of rearing, treatment: F(1,18) = 3.6, p = 0.07; frequency of head dipping, treatment: F(1,18) = 0.2, p = 0.7; frequency of SAP, treatment: F(1,18) = 0.4, p = 0.5; grooming, treatment: F(1,18) = 0.2, p = 0.6). Yet, following the second boost, while all mice spent almost the same amount of time in the open arms (11–12% of the single 5-minutes session, treatment: F(1,18) = 0.09, p = 0.8), GAS mice spent more time rearing compared to CTRL mice (treatment: F(1,18) = 4.54, p = 0.04, see Fig. 4). We did not observe significant between-group differences in the other behavioral parameters considered (frequency of head dipping, treatment: F(1,18) = 1.0, p = 0.3; frequency of SAP, treatment: F(1,18) = 1.5, p = 0.2).


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

Macrì S, Ceci C, Onori MP, Invernizzi RW, Bartolini E, Altabella L, Canese R, Imperi M, Orefici G, Creti R, Margarit I, Magliozzi R, Laviola G - Sci Rep (2015)

Rearing behavior in the elevated 0-maze (week 11, boost 2).The graph shows the duration of rearing behavior (s) in the elevated 0-maze during a 5-minutes long test session performed after the second boost (week 11). GAS mice significantly differ from CTRL mice. *p < 0.05. N = 10 per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548234&req=5

f4: Rearing behavior in the elevated 0-maze (week 11, boost 2).The graph shows the duration of rearing behavior (s) in the elevated 0-maze during a 5-minutes long test session performed after the second boost (week 11). GAS mice significantly differ from CTRL mice. *p < 0.05. N = 10 per group.
Mentions: We evaluated the behavioral profile of naïve subjects on the E0M test after both the first injection (week 5) and the second boost (week 11). Average values and standard errors of all observed data are reported in the supplementary material (see Table 1SM). As expected, experimental subjects showed a remarkable preference for the closed than the open sectors of the maze, whereby they spent approximately 85% of their time in the former and 15% in the latter. Following the first injection, CTRL and GAS mice did not show significant differences in general locomotion (frequency of entries, treatment: F(1,18) = 0.01, p = 0.93), time spent in the open arms (treatment: F(1,18) = 0.01, p = 0.91), and the ethological measures considered (duration of rearing, treatment: F(1,18) = 3.6, p = 0.07; frequency of head dipping, treatment: F(1,18) = 0.2, p = 0.7; frequency of SAP, treatment: F(1,18) = 0.4, p = 0.5; grooming, treatment: F(1,18) = 0.2, p = 0.6). Yet, following the second boost, while all mice spent almost the same amount of time in the open arms (11–12% of the single 5-minutes session, treatment: F(1,18) = 0.09, p = 0.8), GAS mice spent more time rearing compared to CTRL mice (treatment: F(1,18) = 4.54, p = 0.04, see Fig. 4). We did not observe significant between-group differences in the other behavioral parameters considered (frequency of head dipping, treatment: F(1,18) = 1.0, p = 0.3; frequency of SAP, treatment: F(1,18) = 1.5, p = 0.2).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Sect. Behavioural Neuroscience, Dept. Cell Biology &Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Roma, Italy.

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.

No MeSH data available.


Related in: MedlinePlus