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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 impairment in hippocampal cell proliferation. (A) Representative confocal micrographs of DG in the CON (upper left panel), BCG (upper right panel), LPS (lower left panel) and BCG/LPS groups (lower right panel). (B) The bars represent the mean ± SE of the cell number in each group. The data represent the mean ± SE (n=6) and were analyzed using two-way analysis of variance followed by Bonferroni post-hoc test. ** and *** indicate P<0.01 and P<0.001, respectively (post-hoc differences). Scale bar=50 µm. The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; DG, dentate gyrus; CON, control; SE, standard error; PBS, phosphate-buffered saline; BrdU, 5-bromo-2-deoxyuridine.
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f3-mmr-14-02-1574: Neonatal BCG vaccination alleviates LPS-induced impairment in hippocampal cell proliferation. (A) Representative confocal micrographs of DG in the CON (upper left panel), BCG (upper right panel), LPS (lower left panel) and BCG/LPS groups (lower right panel). (B) The bars represent the mean ± SE of the cell number in each group. The data represent the mean ± SE (n=6) and were analyzed using two-way analysis of variance followed by Bonferroni post-hoc test. ** and *** indicate P<0.01 and P<0.001, respectively (post-hoc differences). Scale bar=50 µm. The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; DG, dentate gyrus; CON, control; SE, standard error; PBS, phosphate-buffered saline; BrdU, 5-bromo-2-deoxyuridine.

Mentions: There were significant effects of BCG (F1,20= 6.761; P= 0.0171) and, LPS (F1,20=70.485; P<0.001) and interaction of BCGxLPS (F1,20=6.645; P=0.0180). Subsequent analyses revealed that adult LPS treatment decreased the number of BrdU+ cells (LPS vs. CON group, P<0.001) and that neonatal BCG vaccination attenuated LPS-induced impairment (BCG/LPS vs. LPS group, P=0.0016), although neonatal BCG vaccination alone caused no significant effect (BCG vs. CON group, P=0.9875; Fig. 3).


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 impairment in hippocampal cell proliferation. (A) Representative confocal micrographs of DG in the CON (upper left panel), BCG (upper right panel), LPS (lower left panel) and BCG/LPS groups (lower right panel). (B) The bars represent the mean ± SE of the cell number in each group. The data represent the mean ± SE (n=6) and were analyzed using two-way analysis of variance followed by Bonferroni post-hoc test. ** and *** indicate P<0.01 and P<0.001, respectively (post-hoc differences). Scale bar=50 µm. The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; DG, dentate gyrus; CON, control; SE, standard error; PBS, phosphate-buffered saline; BrdU, 5-bromo-2-deoxyuridine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-14-02-1574: Neonatal BCG vaccination alleviates LPS-induced impairment in hippocampal cell proliferation. (A) Representative confocal micrographs of DG in the CON (upper left panel), BCG (upper right panel), LPS (lower left panel) and BCG/LPS groups (lower right panel). (B) The bars represent the mean ± SE of the cell number in each group. The data represent the mean ± SE (n=6) and were analyzed using two-way analysis of variance followed by Bonferroni post-hoc test. ** and *** indicate P<0.01 and P<0.001, respectively (post-hoc differences). Scale bar=50 µm. The experiment was repeated twice with similar results. BCG, Bacillus Calmette-Guérin; LPS, lipopolysaccharide; DG, dentate gyrus; CON, control; SE, standard error; PBS, phosphate-buffered saline; BrdU, 5-bromo-2-deoxyuridine.
Mentions: There were significant effects of BCG (F1,20= 6.761; P= 0.0171) and, LPS (F1,20=70.485; P<0.001) and interaction of BCGxLPS (F1,20=6.645; P=0.0180). Subsequent analyses revealed that adult LPS treatment decreased the number of BrdU+ cells (LPS vs. CON group, P<0.001) and that neonatal BCG vaccination attenuated LPS-induced impairment (BCG/LPS vs. LPS group, P=0.0016), although neonatal BCG vaccination alone caused no significant effect (BCG vs. CON group, P=0.9875; Fig. 3).

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