In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 1 ( 2021-1-25), p. e0245171-
Kurzfassung:
Infection with Influenza A virus can lead to the development of encephalitis and subsequent neurological deficits ranging from headaches to neurodegeneration. Post-encephalitic parkinsonism has been reported in surviving patients of H1N1 infections, but not all cases of encephalitic H1N1 infection present with these neurological symptoms, suggesting that interactions with an environmental neurotoxin could promote more severe neurological damage. The heavy metal, manganese (Mn), is a potential interacting factor with H1N1 because excessive exposure early in life can induce long-lasting effects on neurological function through inflammatory activation of glial cells. In the current study, we used a two-hit model of neurotoxin-pathogen exposure to examine whether exposure to Mn during juvenile development would induce a more severe neuropathological response following infection with H1N1 in adulthood. To test this hypothesis, C57BL/6 mice were exposed to MnCl 2 in drinking water (50 mg/kg/day) for 30 days from days 21–51 postnatal, then infected intranasally with H1N1 three weeks later. Analyses of dopaminergic neurons, microglia and astrocytes in basal ganglia indicated that although there was no significant loss of dopaminergic neurons within the substantia nigra pars compacta, there was more pronounced activation of microglia and astrocytes in animals sequentially exposed to Mn and H1N1, as well as altered patterns of histone acetylation. Whole transcriptome Next Generation Sequencing (RNASeq) analysis was performed on the substantia nigra and revealed unique patterns of gene expression in the dual-exposed group, including genes involved in antioxidant activation, mitophagy and neurodegeneration. Taken together, these results suggest that exposure to elevated levels of Mn during juvenile development could sensitize glial cells to more severe neuro-immune responses to influenza infection later in life through persistent epigenetic changes.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0245171
DOI:
10.1371/journal.pone.0245171.g001
DOI:
10.1371/journal.pone.0245171.g002
DOI:
10.1371/journal.pone.0245171.g003
DOI:
10.1371/journal.pone.0245171.g004
DOI:
10.1371/journal.pone.0245171.g005
DOI:
10.1371/journal.pone.0245171.t001
DOI:
10.1371/journal.pone.0245171.s001
DOI:
10.1371/journal.pone.0245171.s002
DOI:
10.1371/journal.pone.0245171.s003
DOI:
10.1371/journal.pone.0245171.r001
DOI:
10.1371/journal.pone.0245171.r002
DOI:
10.1371/journal.pone.0245171.r003
DOI:
10.1371/journal.pone.0245171.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2267670-3
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