1. Developmental IL-6 Exposure Favors Production of PDGF-Responsive Multipotential Progenitors at the Expense of Neural Stem Cells and Other Progenitors.
- Author
-
Kumari E, Velloso FJ, Nasuhidehnavi A, Somasundaram A, Savanur VH, Buono KD, and Levison SW
- Subjects
- Animals, Cells, Cultured, DNA (Cytosine-5-)-Methyltransferase 1 genetics, DNA (Cytosine-5-)-Methyltransferase 1 metabolism, F-Box Proteins genetics, F-Box Proteins metabolism, Frontal Lobe cytology, Frontal Lobe metabolism, Interleukin-6 pharmacology, Mice, Mice, Inbred C57BL, Nestin genetics, Nestin metabolism, Neural Stem Cells cytology, Neurogenesis, Neuroglia cytology, Neuroglia metabolism, Pluripotent Stem Cells drug effects, Pluripotent Stem Cells metabolism, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, STAT3 Transcription Factor metabolism, Cell Lineage, Frontal Lobe growth & development, Interleukin-6 metabolism, Neural Stem Cells metabolism, Platelet-Derived Growth Factor metabolism, Pluripotent Stem Cells cytology
- Abstract
Interleukin-6 (IL-6) is increased in maternal serum and amniotic fluid of children subsequently diagnosed with autism spectrum disorders. However, it is not clear how increased IL-6 alters brain development. Here, we show that IL-6 increases the prevalence of a specific platelet-derived growth factor (PDGF)-responsive multipotent progenitor, with opposite effects on neural stem cells and on subsets of bipotential glial progenitors. Acutely, increasing circulating IL-6 levels 2-fold above baseline in neonatal mice specifically stimulated the proliferation of a PDGF-responsive multipotential progenitor accompanied by increased phosphorylated STAT3, increased Fbxo15 expression, and decreased Dnmt1 and Tlx expression. Fate mapping studies using a Nestin-CreERT2 driver revealed decreased astrogliogenesis in the frontal cortex. IL-6-treated mice were hyposmic; however, olfactory bulb neuronogenesis was unaffected. Altogether, these studies provide important insights into how inflammation alters neural stem cells and progenitors and provide new insights into the molecular and cellular underpinnings of neurodevelopmental disorders associated with maternal infections., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF