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Neonatal Bacillus Calmette-Guérin vaccination alleviates lipopolysaccharide-induced neurobehavioral impairments and neuroinflammation in adult mice.

Yang J, Qi F, Yao Z - Mol Med Rep (2016)

Bottom Line: The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood.However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood.In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.

ABSTRACT
The Bacillus Calmette-Guérin (BCG) vaccine is routinely administered to human neonates worldwide. BCG has recently been identified as a neuroprotective immune mediator in several neuropathological conditions, exerting neuroprotection in a mouse model of Parkinson's disease and slowing the progression of clinically isolated syndrome in patients with multiple sclerosis. The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood. However, whether the neonatal BCG vaccination affects the brain in adulthood remains to be elucidated. In the present study, newborn C57BL/6 mice were injected subcutaneously with BCG (105 colony forming units) or phosphate‑buffered saline (PBS). A total of 12 weeks later, the mice were injected intraperitoneally with 330 µg/kg lipopolysaccharide (LPS) or PBS. The present study reported that the neonatal BCG vaccination alleviated sickness, anxiety and depression‑like behavior, lessened the impairments in hippocampal cell proliferation and downregulated the proinflammatory responses in the serum and brain that were induced by the adult LPS challenge. However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood. In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood.

No MeSH data available.


Related in: MedlinePlus

Neonatal BCG vaccination alleviates LPS-induced depression and anxiety-like behavior in adulthood. The mice were subjected to the FST and TST tasks 30 min prior to LPS injection and 4, 8, and 24 h later. The bars represent the mean immobility time spent in the (A) FST and (B) TST tasks. The data were analyzed using three-way (BCGxLPSxtime) repeated measures ANOVA followed by Bonferroni post-hoc test. The mice were subjected to the OFT task 2.5 h subsequent to LPS injection. The bars represent the mean (C) locomotor activities, (D) rearing activities and the (E) proportion of center zone activities by mice during the 30-min test. For each of the three behavior tests, a new set of animals were used to avoid possible disturbances. The data represent the mean ± SE (n=16) and were analyzed using two-way ANOVA followed by Bonferroni post-hoc test. The symbols '*', '#' and '&' indicate significant differences compared with the CON mice, BCG group and LPS group, respectively. The single, double and triple symbols indicate P<0.05, P<0.01 and P<0.001, respectively (post-hoc differences). The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; FST, forced swimming test; TST, tail suspension test; ANOVA, analysis of variance; OFT, open field test; SE, standard error; CON, control.
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f2-mmr-14-02-1574: Neonatal BCG vaccination alleviates LPS-induced depression and anxiety-like behavior in adulthood. The mice were subjected to the FST and TST tasks 30 min prior to LPS injection and 4, 8, and 24 h later. The bars represent the mean immobility time spent in the (A) FST and (B) TST tasks. The data were analyzed using three-way (BCGxLPSxtime) repeated measures ANOVA followed by Bonferroni post-hoc test. The mice were subjected to the OFT task 2.5 h subsequent to LPS injection. The bars represent the mean (C) locomotor activities, (D) rearing activities and the (E) proportion of center zone activities by mice during the 30-min test. For each of the three behavior tests, a new set of animals were used to avoid possible disturbances. The data represent the mean ± SE (n=16) and were analyzed using two-way ANOVA followed by Bonferroni post-hoc test. The symbols '*', '#' and '&' indicate significant differences compared with the CON mice, BCG group and LPS group, respectively. The single, double and triple symbols indicate P<0.05, P<0.01 and P<0.001, respectively (post-hoc differences). The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; FST, forced swimming test; TST, tail suspension test; ANOVA, analysis of variance; OFT, open field test; SE, standard error; CON, control.

Mentions: The mice were subjected to the FST and TST tasks 30 min prior to, and 4, 8 and 24 h following, LPS injection. A three-way (BCGxLPSxtime) ANOVA of the FST data revealed significant effects of BCG (F1,60=31.42; P<0.001), LPS (F1,60=125.44; P<0.001) and time (F3,180=36.13; P<0.001), and significant interactions of BCGxLPS (F1,60=28.26; P<0.001), BCGxtime (F3,180=3.01; P=0.0316), LPSxtime (F3,180=36.26; P<0.001) and BCGxLPSxtime (F3,180=4.86; P=0.0028). Subsequent analyses revealed that adult LPS treatment increased the immobility time of mice (LPS vs. CON group, P<0.001) and that neonatal BCG vaccination significantly attenuated the LPS-induced increase (BCG/LPS vs. LPS group, P<0.001; Fig. 2A).


Neonatal Bacillus Calmette-Guérin vaccination alleviates lipopolysaccharide-induced neurobehavioral impairments and neuroinflammation in adult mice.

Yang J, Qi F, Yao Z - Mol Med Rep (2016)

Neonatal BCG vaccination alleviates LPS-induced depression and anxiety-like behavior in adulthood. The mice were subjected to the FST and TST tasks 30 min prior to LPS injection and 4, 8, and 24 h later. The bars represent the mean immobility time spent in the (A) FST and (B) TST tasks. The data were analyzed using three-way (BCGxLPSxtime) repeated measures ANOVA followed by Bonferroni post-hoc test. The mice were subjected to the OFT task 2.5 h subsequent to LPS injection. The bars represent the mean (C) locomotor activities, (D) rearing activities and the (E) proportion of center zone activities by mice during the 30-min test. For each of the three behavior tests, a new set of animals were used to avoid possible disturbances. The data represent the mean ± SE (n=16) and were analyzed using two-way ANOVA followed by Bonferroni post-hoc test. The symbols '*', '#' and '&' indicate significant differences compared with the CON mice, BCG group and LPS group, respectively. The single, double and triple symbols indicate P<0.05, P<0.01 and P<0.001, respectively (post-hoc differences). The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; FST, forced swimming test; TST, tail suspension test; ANOVA, analysis of variance; OFT, open field test; SE, standard error; CON, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940080&req=5

f2-mmr-14-02-1574: Neonatal BCG vaccination alleviates LPS-induced depression and anxiety-like behavior in adulthood. The mice were subjected to the FST and TST tasks 30 min prior to LPS injection and 4, 8, and 24 h later. The bars represent the mean immobility time spent in the (A) FST and (B) TST tasks. The data were analyzed using three-way (BCGxLPSxtime) repeated measures ANOVA followed by Bonferroni post-hoc test. The mice were subjected to the OFT task 2.5 h subsequent to LPS injection. The bars represent the mean (C) locomotor activities, (D) rearing activities and the (E) proportion of center zone activities by mice during the 30-min test. For each of the three behavior tests, a new set of animals were used to avoid possible disturbances. The data represent the mean ± SE (n=16) and were analyzed using two-way ANOVA followed by Bonferroni post-hoc test. The symbols '*', '#' and '&' indicate significant differences compared with the CON mice, BCG group and LPS group, respectively. The single, double and triple symbols indicate P<0.05, P<0.01 and P<0.001, respectively (post-hoc differences). The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; FST, forced swimming test; TST, tail suspension test; ANOVA, analysis of variance; OFT, open field test; SE, standard error; CON, control.
Mentions: The mice were subjected to the FST and TST tasks 30 min prior to, and 4, 8 and 24 h following, LPS injection. A three-way (BCGxLPSxtime) ANOVA of the FST data revealed significant effects of BCG (F1,60=31.42; P<0.001), LPS (F1,60=125.44; P<0.001) and time (F3,180=36.13; P<0.001), and significant interactions of BCGxLPS (F1,60=28.26; P<0.001), BCGxtime (F3,180=3.01; P=0.0316), LPSxtime (F3,180=36.26; P<0.001) and BCGxLPSxtime (F3,180=4.86; P=0.0028). Subsequent analyses revealed that adult LPS treatment increased the immobility time of mice (LPS vs. CON group, P<0.001) and that neonatal BCG vaccination significantly attenuated the LPS-induced increase (BCG/LPS vs. LPS group, P<0.001; Fig. 2A).

Bottom Line: The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood.However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood.In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.

ABSTRACT
The Bacillus Calmette-Guérin (BCG) vaccine is routinely administered to human neonates worldwide. BCG has recently been identified as a neuroprotective immune mediator in several neuropathological conditions, exerting neuroprotection in a mouse model of Parkinson's disease and slowing the progression of clinically isolated syndrome in patients with multiple sclerosis. The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood. However, whether the neonatal BCG vaccination affects the brain in adulthood remains to be elucidated. In the present study, newborn C57BL/6 mice were injected subcutaneously with BCG (105 colony forming units) or phosphate‑buffered saline (PBS). A total of 12 weeks later, the mice were injected intraperitoneally with 330 µg/kg lipopolysaccharide (LPS) or PBS. The present study reported that the neonatal BCG vaccination alleviated sickness, anxiety and depression‑like behavior, lessened the impairments in hippocampal cell proliferation and downregulated the proinflammatory responses in the serum and brain that were induced by the adult LPS challenge. However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood. In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood.

No MeSH data available.


Related in: MedlinePlus