Chronic glucocorticoid exposure suppressed the differentiation and survival of embryonic neural stem/progenitor cells: Possible involvement of ERK and PI3K/Akt signaling in the neuronal differentiation

Haruki Odaka, Tadahiro Numakawa, Aya Yoshimura, Shingo Nakajima, Naoki Adachi, Yoshiko Ooshima, Takafumi Inoue, Hiroshi Kunugi

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Growing evidence suggests that excess glucocorticoids (GCs) exposure during the pregnancy results in behavioral abnormality in offspring. Although research using animal models has demonstrated that systemic GCs treatment impairs development of fetal brain, direct impact of GCs on the phenotype of embryonic neural stem/progenitor cells (eNSPCs) and its mechanism has not been fully understood. Here, we investigated the effect of chronic GCs exposure on cell proliferation, differentiation, and survival of eNSPCs in vitro. Corticosterone (CORT, a murine GC) treatment did not affect the proliferation of eNSPCs. On the other hand, decreased expression of neuronal, synaptic, and astroglial marker proteins were observed when the differentiation of eNSPCs was induced in the presence of CORT. CORT also reduced the survival rate of eNSPCs after the differentiation. Moreover, CORT inhibited extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathways, which were activated during cell differentiation of eNSPCs. Inhibiting these signaling pathways reduced neural differentiation and eNSPCs viability, indicating their essential roles in the eNSPCs differentiation. Furthermore, IGF-I, a potent PI3K/Akt and ERK signaling stimulator, partially restored the adverse effect of CORT on eNSPCs, suggesting a possible involvement of the repression of these intracellular signaling in the GCs-caused eNSPCs impairment.

    Original languageEnglish
    JournalNeuroscience Research
    DOIs
    Publication statusAccepted/In press - 2015 Dec 22

    Keywords

    • Cell survival
    • Corticosterone
    • Differentiation
    • Extracellular signal-regulated kinase
    • Glucocorticoid
    • Neural stem cell
    • Phosphatidylinositol 3-kinase

    ASJC Scopus subject areas

    • Neuroscience(all)

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