OLIGODENDROCYTES MATURATION AND METABOLIC PROFILE UPON IRON DEFICIENCY

ROSATO-SIRI, M. V; MORELLI, L.; GUITART, M. E.; VERSTRAETEN, S. V.; MARTINO ADAMI, P. V.; PASQUINI, J. M.

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Sociedades de Biociencias

Iron defciency (ID) represents one of the most prevalent nutritional defcits, affecting almost two billion people worldwide. Gestational iron deprivation as an experimental model is a useful tool to describe specifc oligodendrocyte (OL) requirements for progressionto a mature and myelinating state. Previous work demonstrated that ID-OL appear to exhibit intrinsic alterations in terms of proliferation, migration and maturation. To better understand OL maturation, we explore the hypothesis that ID constrains OL maturation by impairing metabolic pathways. In vivo and in vitro studies were conducted to evaluate: a) OL lineage composition along ontogenetic myelination; b) OL lineage cell number regulation; c) Glial cell metabolic profles. We used an eGFP::CNPase transgenic mouse which renders the whole OL-lineage-committed cells as green-fluorescent (CNPase-positive cells). Pregnant mice were fed an ID diet (4mg/g/kg) as from gestational day 5. Postnatal development of myelination was evaluated 15 and 30 days after birth (PND15 and 30). At PND15, ID-OL lineage exhibited an increase in CNPase-positive cells but this redundancy failed to attain complexity and maturity (p≤ 0.01). At PND30, the number of CNPase-positive cells decreased, through an increase in cell death (p≤ 0.01). To further describe ID effects, the correlation was explored between maturational stage and ID metabolic signature. Energy metabolism was assessed in OL and astrocyte (AST) primary cultures from newly born ID WT pups. Measurements of glycolysis and mitochondrial respiration showed that ID glial cell (OL and AST) maximum rate of respiration was lower than control ones (p≤ 0.001). In addition, control AST exhibited a higher basal glycolitic capacity than ID AST (p≤ 0.001). These fndings further prove that the regulation of cell metabolism may impact cell fate decisions and maturational status.