NF-κB Signaling in Astrocytes Modulates Brain Inflammation and Neuronal Injury Following Sequential Exposure to Manganese and MPTP During Development and Aging.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Sean L HammondRonald B Tjalkens

Abstract

Chronic exposure to manganese (Mn) is associated with neuroinflammation and extrapyramidal motor deficits resembling features of Parkinson's disease. Activation of astrocytes and microglia is implicated in neuronal injury from Mn but it is not known whether early life exposure to Mn may predispose glia to more severe inflammatory responses during aging. We therefore examined astrocyte nuclear factor kappa B (NF-κB) signaling in mediating innate immune inflammatory responses during multiple neurotoxic exposures spanning juvenile development into adulthood. MnCl2 was given in drinking water for 30-day postweaning to both wildtype mice and astrocyte-specific knockout (KO) mice lacking I kappa B kinase 2, the central upstream activator of NF-κB. Following juvenile exposure to Mn, mice were subsequently administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 4 months of age. Animals were evaluated for behavioral alterations and brain tissue was analyzed for catecholamine neurotransmitters. Stereological analysis of neuronal and glial cell counts from multiple brain regions indicated that juvenile exposure to Mn amplified glial activation and neuronal loss from MPTP exposure in the caudate-putamen and globus pallidus, as ...Continue Reading

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Citations

Jan 10, 2021·Seminars in Cell & Developmental Biology·Qian WuFudi Wang
Jan 8, 2021·Brain Research·Baoman LiAlexei Verkhratsky
Dec 11, 2020·Cells·Ikuko Miyazaki, Masato Asanuma
May 1, 2021·International Journal of Molecular Sciences·Alexey A TinkovMichael Aschner
May 29, 2021·Neurochemistry International·Yan-Ying Fan, Jing Huo

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