TY - JOUR
T1 - Chronic glucocorticoid exposure suppressed the differentiation and survival of embryonic neural stem/progenitor cells
T2 - Possible involvement of ERK and PI3K/Akt signaling in the neuronal differentiation
AU - Odaka, Haruki
AU - Numakawa, Tadahiro
AU - Yoshimura, Aya
AU - Nakajima, Shingo
AU - Adachi, Naoki
AU - Ooshima, Yoshiko
AU - Inoue, Takafumi
AU - Kunugi, Hiroshi
N1 - Funding Information:
This project was supported by grants from by Takeda Science Foundation (T.N.), and from the Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI JP16K06996) (T.N.) in the Ministry of Education, Culture, Sports, Science, and Technology of Japan. This study was also supported by the Health and Labor Sciences Research Grants (H.K.), Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP (H.K.) and CREST, Japan Science and Technology Agency (JST) (T.N., N.A. and H.K.).
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neures.2016.07.002
DO - 10.1016/j.neures.2016.07.002
M3 - Article
C2 - 27432545
AN - SCOPUS:84992413241
VL - 113
SP - 28
EP - 36
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
ER -