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(+) apoptosis but did not dramatically affect PCNA(+) 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.
authors: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
authors: Ya
authors: Y
authors: Jin
authors: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors: Guang
authors: G
authors: Wang
authors: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
authors: Sha-Sha
authors: SS
authors: Han
authors: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
authors: Mei-Yao
authors: MY
authors: He
authors: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors: Xin
authors: X
authors: Cheng
authors: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors: Zheng-Lai
authors: ZL
authors: Ma
authors: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
authors: Xia
authors: X
authors: Wu
authors: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors: Xuesong
authors: X
authors: Yang
authors: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China. Electronic address: tlgs@jnu.edu.cn.
authors: Guo-Sheng
authors: GS
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000633:toxicity; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D018809:Proliferating Cell Nuclear Antigen; D014404:Tubulin; C462941:beta3 tubulin, mouse; D005947:Glucose
keywords: Neurodevelopmental defects; Nrf2 signalling; Oxidative stress; PGDM