Characterization of a population of neural progenitor cells in the infant hippocampus

Simon M L Paine,Sarah L Nicholson,Thomas S Jacques,Alex R Willsher,Neil J Sebire

doi:10.1111/nan.12065

Abstract

AimsAbnormalities of the hippocampus are associated with a range of diseases in children, including epilepsy and sudden death. A population of rod cells in part of the hippocampus, the polymorphic layer of the dentate gyrus, has long been recognized in infants. Previous work suggested that these cells were microglia and that their presence was associated with chronic illness and sudden infant death syndrome. Prompted by the observations that a sensitive immunohistochemical marker of microglia used in diagnostic practice does not typically stain these cells and that the hippocampus is a site of postnatal neurogenesis, we hypothesized that this transient population of cells were not microglia but neural progenitors.MethodsUsing archived post mortem tissue, we applied a broad panel of antibodies to establish the immunophenotype of these cells in 40 infants dying suddenly of causes that were either explained or remained unexplained, following post mortem investigation.ResultsThe rod cells were consistently negative for the microglial markers CD45, CD68 and HLA-DR. The cells were positive, in varying proportions, for the neural progenitor marker, doublecortin, the neural stem cell marker, nestin and the neural marker, TUJ1.ConclusionsThese data support our hypothesis that the rod cells of the polymorphic layer of the dentate gyrus in the infant hippocampus are not microglia but a population of neural progenitors. These findings advance our understanding of postnatal neurogenesis in the human hippocampus in health and disease and are of diagnostic importance, allowing reactive microglia to be distinguished from the normal population of neural progenitors.

Highlights

Abnormalities of the hippocampus have been linked to a range of pathological states in children, including epilepsy [1] and sudden death [2,3]
On the basis of morphology, lectin histochemistry and immunohistochemistry for HAM56, it has been reported that these rod cells in the polymorphic layer (PML) of infants were microglia [5].These cells were rarely seen beyond 9 months of corrected age and were more frequent in infants dying of a range of chronic hypoxic or hypotensive states and in sudden infant death syndrome (SIDS) [5] than in infants dying of acute causes
The rod cells of the PML of the dentate gyrus (DG) are consistently negative for three sensitive immunohistochemical markers of microglia

Summary

Introduction

Abnormalities of the hippocampus have been linked to a range of pathological states in children, including epilepsy [1] and sudden death [2,3]. On the basis of morphology (including ultrastructure), lectin histochemistry and immunohistochemistry for HAM56, it has been reported that these rod cells in the PML of infants were microglia [5].These cells were rarely seen beyond 9 months of corrected age and were more frequent in infants dying of a range of chronic hypoxic or hypotensive states and in sudden infant death syndrome (SIDS) [5] than in infants dying of acute causes. The presence of these characteristic cells in the PML of infants dying suddenly has since been interpreted as evidence of hypoxic/ischaemic injury [6,7]. The finding in the initial report that rod cells were not seen

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Conclusion