Oligodendrocyte Response to Pathophysiological Conditions Triggered by Episode of Perinatal Hypoxia-Ischemia: Role of IG
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ORIGINAL ARTICLE
Oligodendrocyte Response to Pathophysiological Conditions Triggered by Episode of Perinatal Hypoxia-Ischemia: Role of IGF-1 Secretion by Glial Cells Justyna Janowska 1 & Justyna Gargas 1 & Malgorzata Ziemka-Nalecz 1 & Teresa Zalewska 1 & Joanna Sypecka 1 Received: 16 April 2020 / Accepted: 8 July 2020 # The Author(s) 2020
Abstract Differentiation of oligodendrocyte progenitors towards myelinating cells is influenced by a plethora of exogenous instructive signals. Insulin-like growth factor 1 (IGF-1) is one of the major factors regulating cell survival, proliferation, and maturation. Recently, there is an ever growing recognition concerning the role of autocrine/paracrine IGF-1 signaling in brain development and metabolism. Since oligodendrocyte functioning is altered after the neonatal hypoxic-ischemic (HI) insult, a question arises if the injury exerts any influence on the IGF-1 secreted by neural cells and how possibly the change in IGF-1 concentration affects oligodendrocyte growth. To quantify the secretory activity of neonatal glial cells, the step-wise approach by sequentially using the in vivo, ex vivo, and in vitro models of perinatal asphyxia was applied. A comparison of the results of in vivo and ex vivo studies allowed evaluating the role of autocrine/paracrine IGF-1 signaling. Accordingly, astroglia were indicated to be the main local source of IGF-1 in the developing brain, and the factor secretion was shown to be significantly upregulated during the first 24 h after the hypoxic-ischemic insult. And conversely, the IGF-1 amounts released by oligodendrocytes and microglia significantly decreased. A morphometric examination of oligodendrocyte differentiation by means of the Sholl analysis showed that the treatment with low IGF-1 doses markedly improved the branching of oligodendroglial cell processes and, in this way, promoted their differentiation. The changes in the IGF-1 amounts in the nervous tissue after HI might contribute to the resulting white matter disorders, observed in newborn children who experienced perinatal asphyxia. Pharmacological modulation of IGF-1 secretion by neural cells could be reasonable solution in studies aimed at searching for therapies alleviating the consequences of perinatal asphyxia. Keywords Glial cells . Oligodendrocyte maturation . Astrocytes . Microglia . Neural development . Perinatal asphyxia . Neonatal hypoxia-ischemia . IGF-1 secretion . Autocrine/paracrine effect . Sholl analysis of cell branching
Introduction To acquire the ability to myelinate the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs, so called NG2-glia) have to undergo a multistage differentiation process, which is guided by a plethora of extracellular instructive signals. Some of them are known to guide OPCs migration, like for instance the activity of metalloproteinases which help to reorganize the extracellular matrix and facilitate cell * Joanna Sypecka [email protected] 1
NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of
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