No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.ĭrug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory.Ĭopyright: All rights reserved. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. By 18DIV, partial recovery of the dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and the length of branches. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons were reduced. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e. Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a degree of neuronal ID similar to that seen in rodent ID models. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status.

Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching.

ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide.

Neuron dendrite