Oligodendrocyte maturation through gestational iron depravation: The road not taken

MARIA EUGENIA GUITART; MARIA VICTORIA ROSATO-SIRI; MARIANELA VENCE; JUANA MARIA PASQUINI

Mar del Plata

Congreso; Congreso XXX SAN; 2015

Sociedad Argentina de Neurociencia

Oligodendrocyte maturation through gestational iron deprivation: the road not takenMaría Eugenia Guitart, María Victoria Rosato-Siri, Marianela Vence, Juana María PasquiniDepartamento de Química Biológica, IQUIFIB-CONICET. FFyB. UBA. Buenos Aires. ArgentinaAbstract Iron deficiency (ID) is, according to the WHO, the most common nutritional deficiency in the world and the second one in economic impact. This deficiency affects oligodendrocyte (OL) maturation, causing hypomyelination which continues in adulthood even after normal iron diet reinstatement. In this context, our fundamental aim is to elucidate the role of iron during OL maturation and myelination processes. We have previously demonstrated that gestational ID produces alterations in myelin composition, abnormal migration and maturation of oligodendroglial precursor cells (OPC) and altered myelin structure. To further describe the whole population of OL, we have now focused on four aspects: a) OL morphological architecture, which reflects OL maturation, b) the timing of dysmyelination in different brain areas, c) the expression pattern of markers for different stages of OL lineage along ontogenetic myelination and d) OL interaction with different cell types within normal CNS cytoarchitecture, such as relative abundance of GAP junction proteins and astrocyte distribution pattern. To this end, we used an eGFP::CNPase transgenic mouse experimental model, whose green-fluorescent OL-lineage-committed cells (CNPase-positive cells) allow the visualization of the entire myelin structure, as well as the analysis of single OL morphology and population features. Pregnant mice were fed an iron-deficient diet (4mg/g/kg) as from gestational day 5 until pup weaning (post-natal day 21, P21). Plates within the anterior-posterior axis were evaluated at P15 and 30, and CNPase-positive cell distribution was quantified in pre-frontal cortex, corpus striatum and corpus callosum. Control animals evidenced an increase in OL complexity both during ontogenetic development and along the anterior-posterior axis; in particular, OL population exhibited the greatest mature proportion at posterior position. In turn, ID animals exhibited fewer CNPase-positive cells, with prevalence of immature OL, as tested by specific markers and confirmed by a decrease in MBP expression. We conclude that low iron availability does not affect cell lineage specification but expands an arrested OPC population, which is responsible for hypomyelination.