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Title: Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model

Abstract

Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel{sup +} apoptosis but did not dramatically affect PCNA{sup +} cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, themore » data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. - Highlights: • Typical neurodevelopmental defects could be observed in STZ-treated mouse fetuses. • Nrf2 played a crucial role in hyperglycaemia-induced brain malformations. • The effects of hyperglycaemia on neurons and glia cells were not same.« less

Authors:
 [1];  [2]; ;  [1]; ;  [2];  [1];  [2];  [1]
  1. Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China (China)
  2. Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632 (China)
Publication Date:
OSTI Identifier:
22649761
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 347; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; ANTIOXIDANTS; APOPTOSIS; BRAIN; CELL PROLIFERATION; CONCENTRATION RATIO; CONTROL; DIABETES MELLITUS; FETUSES; GLUCOSE; HAZARDS; MALFORMATIONS; MICE; NERVE CELLS; OXIDATION; STREPTOZOCIN; SUPEROXIDE DISMUTASE; VIABILITY

Citation Formats

Jin, Ya, Wang, Guang, Han, Sha-Sha, He, Mei-Yao, Cheng, Xin, Ma, Zheng-Lai, Wu, Xia, Yang, Xuesong, E-mail: yang_xuesong@126.com, and Liu, Guo-Sheng, E-mail: tlgs@jnu.edu.cn. Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.08.002.
Jin, Ya, Wang, Guang, Han, Sha-Sha, He, Mei-Yao, Cheng, Xin, Ma, Zheng-Lai, Wu, Xia, Yang, Xuesong, E-mail: yang_xuesong@126.com, & Liu, Guo-Sheng, E-mail: tlgs@jnu.edu.cn. Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model. United States. doi:10.1016/J.YEXCR.2016.08.002.
Jin, Ya, Wang, Guang, Han, Sha-Sha, He, Mei-Yao, Cheng, Xin, Ma, Zheng-Lai, Wu, Xia, Yang, Xuesong, E-mail: yang_xuesong@126.com, and Liu, Guo-Sheng, E-mail: tlgs@jnu.edu.cn. 2016. "Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model". United States. doi:10.1016/J.YEXCR.2016.08.002.
@article{osti_22649761,
title = {Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model},
author = {Jin, Ya and Wang, Guang and Han, Sha-Sha and He, Mei-Yao and Cheng, Xin and Ma, Zheng-Lai and Wu, Xia and Yang, Xuesong, E-mail: yang_xuesong@126.com and Liu, Guo-Sheng, E-mail: tlgs@jnu.edu.cn},
abstractNote = {Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel{sup +} apoptosis but did not dramatically affect PCNA{sup +} cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. - Highlights: • Typical neurodevelopmental defects could be observed in STZ-treated mouse fetuses. • Nrf2 played a crucial role in hyperglycaemia-induced brain malformations. • The effects of hyperglycaemia on neurons and glia cells were not same.},
doi = {10.1016/J.YEXCR.2016.08.002},
journal = {Experimental Cell Research},
number = 1,
volume = 347,
place = {United States},
year = 2016,
month = 9
}
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