Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord

Abstract

Spina bifida, which results from failure of fusion in the spinal region of neural tube, is among the most common birth defects associated with diabetic pregnancy. However, the mechanism underlying maternal diabetes-induced congenital malformations including spina bifida is not fully understood. It was hypothesized that hyperglycemic conditions affect the proliferation and apoptosis of neural progenitor cells in the developing spinal neural tube, leading to abnormal neurodevelopment. In the present study, biological processes such as proliferation and apoptosis were investigated in the neuroepithelial cells of the developing spinal neural tube of embryos from diabetic mice, and in embryonic spinal neural tube derived neural progenitor cell cultures exposed to high glucose in vitro. Maternal diabetes caused decreased proliferation and increased apoptosis of the neuroepithelial cells in the developing spinal cord of embryos from diabetic mouse. Decreased proliferation and increased apoptosis were also found in neural progenitor cells exposed to high glucose. In addition, high glucose-induced apoptosis in neural progenitor cells was associated with activation of caspase-3. Thus, high glucose disturbs both proliferation and cell death of neural progenitors in the developing spinal neural tube. This could provide a cellular mechanism by which maternal hyperglycemia induces spina bifida in embryos from diabetic pregnancy.

Diabetes and apoptosis: neural crest cells and neural tube

“…For example, increased numbers of apoptotic cells have been observed within the fused neural tubes of day 11.5–13.5 mouse embryos [105–107]. However, these observations of apoptosis were scattered, and were observed after neural tube fusion, suggesting that they may be involved in further maturation of the CNS, rather than NTD.…”

Maternal Diabetes Increases Small Conductance Ca2+-Activated K+(SK) Currents That Alter Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

“…Maternal diabetes decreases proliferation and increases apoptosis of neuroepithelial cells in the developing spinal cords of embryos from streptozotocin (STZ)-induced diabetic (type 1) mouse mothers (Gao and Gao 2007). Fetal hyperglycemia exposure may promote neural malformation via oxidative stress (Hockett et al 2004).…”

Down regulation of the Proliferation and Apoptotic Pathways in the Embryonic Brain of Diabetic Rats

“…The human brain is particularly vulnerable to the effects of hyperglycemia, and the relative risk of central nervous system malformations is 15.5 times higher than in normal pregnancies (Cannon et al 2002). Previous studies have shown an increased rate of apoptosis and a decreased index of neuronal proliferation during organogenesis associated with disturbed embryonic maturation, increased embryonic resorption and congenital malformations (Gao and Gao 2007;Sun et al 2005;Zhao et al 2009). The results of the present study expand upon these findings by showing that exposure to uncontrolled gestational hyperglycemia can disrupt both neuronal proliferation and neuronal survival in non-malformed embryos from STZ-induced diabetic rats.…”