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Long‐term impact of neonatal inflammation on demyelination and remyelination in the central nervous system
Author(s) -
Bénardais Karelle,
Gudi Viktoria,
Gai Lijie,
Neßler Jasmin,
Singh Vikramjeet,
Prajeeth Chittappen K.,
Skripuletz Thomas,
Stangel Martin
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22706
Subject(s) - remyelination , neuroscience , biology , central nervous system , inflammation , term (time) , immunology , myelin , physics , quantum mechanics
Perinatal inflammation causes immediate changes of the blood‐brain barrier (BBB) and thus may have different consequences in adult life including an impact on neurological diseases such as demyelinating disorders. In order to determine if such a perinatal insult affects the course of demyelination in adulthood as “second hit,” we simulated perinatal bacterial inflammation by systemic administration of lipopolysaccharide (LPS) to either pregnant mice or newborn animals. Demyelination was later induced in adult animals by cuprizone [ bis (cyclohexylidenehydrazide)], which causes oligodendrocyte death with subsequent demyelination accompanied by strong microgliosis and astrogliosis. A single LPS injection at embryonic day 13.5 did not have an impact on demyelination in adulthood. In contrast, serial postnatal LPS injections (P0‐P8) caused an early delay of myelin removal in the corpus callosum, which was paralleled by reduced numbers of activated microglia. During remyelination, postnatal LPS treatment enhanced early remyelination with a concomitant increase of mature oligodendrocytes. Furthermore, the postnatal LPS challenge impacts the phenotype of microglia since an elevated mRNA expression of microglia related genes such as TREM 2, CD11b, TNF‐α, TGF‐β1, HGF, FGF‐2, and IGF‐1 was found in these preconditioned mice during early demyelination. These data demonstrate that postnatal inflammation has long‐lasting effects on microglia functions and modifies the course of demyelination and remyelination in adulthood. GLIA 2014;62:1659–1670