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Depletion of the neural precursor cell pool by glucocorticoids
Author(s) -
Yu Shuang,
Patchev Alexandre V.,
Wu Yan,
Lu Jie,
Holsboer Florian,
Zhang JingZhong,
Sousa Nuno,
Almeida Osborne F. X.
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21812
Subject(s) - dentate gyrus , neurogenesis , hippocampal formation , neural stem cell , progenitor cell , population , neuroscience , biology , hippocampus , nestin , glucocorticoid , precursor cell , stem cell , bromodeoxyuridine , endocrinology , medicine , microbiology and biotechnology , cell , immunology , immunohistochemistry , genetics , environmental health
Objective Glucocorticoids (GCs) are indicated for a number of conditions in obstetrics and perinatal medicine; however, the neurodevelopmental and long‐term neurological consequences of early‐life GC exposure are still largely unknown. Preclinical studies have demonstrated that GCs have a major influence on hippocampal cell turnover by inhibiting neurogenesis and stimulating apoptosis of mature neurons. Here we examined the fate of the limited pool of neural progenitor cells (NPCs) after GC administration during neonatal development; the impact of this treatment on hippocampal structure was also studied. Methods Phenotype‐specific genetic and antigenic markers were used to identify cultured NPCs at various developmental stages; the survival of these cells was monitored after exposure to the synthetic glucocorticoid dexamethasone (DEX). In addition, the effects of neonatal DEX treatment on the neurogenic potential of the rat hippocampus were examined by monitoring the incorporation of bromodeoxyuridine and expression of Ki67 antigen at various postnatal ages. Results Multipotent nestin‐expressing NPCs and Tα1‐tubulin–expressing immature neurons succumb to GC‐induced apoptosis in primary hippocampal cultures. Neonatal GC treatment results in marked apoptosis among the proliferating population of cells in the dentate gyrus, depletes the NPC pool, and leads to significant and sustained reductions in the volume of the dentate gyrus. Interpretation Both NPCs and immature neurons in the hippocampus are sensitive to the proapoptotic actions of GCs. Depletion of the limited NPC pool during early life retards hippocampal growth, thus allowing predictions about the potential neurological and psychiatric consequences of neonatal GC exposure. ANN NEUROL 2010;67:21–30