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iScience. 2019 Jul 29;19:303-315. doi: 10.1016/j.isci.2019.07.038. [Epub ahead of print]

CNTF and Nrf2 Are Coordinately Involved in Regulating Self-Renewal and Differentiation of Neural Stem Cell during Embryonic Development.

Author information

1
Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
2
International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
3
Department of Anatomy and Molecular Embryology, Ruhr University Bochum, Bochum, Germany.
4
International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
5
Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China. Electronic address: tlgs@jnu.edu.cn.

Abstract

There is high risk of fetal neurodevelopmental defects in pregestational diabetes mellitus (PGDM). However, the effective mechanism of hyperglycemia-induced neurodevelopmental negative effects, including neural stem cell self-renewal and differentiation, still remains obscure. Neuropoietic cytokines have been shown to play a vital part during nervous system development and in the coordination of neurons and gliocytes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) dysfunction might be related to a reduction of self-protective response in brain malformation induced by hyperglycemia. We therefore evaluated the role of Nrf2 and neuropoietic cytokines in fetal neurodevelopmental defects induced by PGDM and determined the mechanisms involved. Our data reveal that PGDM dramatically impairs the developmental switch of neural stem cells from neurogenesis to gliogenesis, principally under the cooperative mediation of neuropoietic cytokine CNTF and Nrf2 antioxidative signaling. This indicates that CNTF and Nrf2 could be potentially used in the prevention or therapy of neurodevelopmental defects of PGDM offspring.

KEYWORDS:

Developmental Neuroscience; Diabetology; Molecular Neuroscience

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