TY - JOUR
T1 - Maternal Diabetes Deregulates the Expression of Mecp2 via miR-26b-5p in Mouse Embryonic Neural Stem Cells
AU - Shyamasundar, Sukanya
AU - Ramya, Seshadri
AU - Kandilya, Deepika
AU - Srinivasan, Dinesh Kumar
AU - Bay, Boon Huat
AU - Ansari, Suraiya Anjum
AU - Dheen, S. Thameem
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/6
Y1 - 2023/6
N2 - Maternal diabetes has been associated with a greater risk of neurodevelopmental disorders in offspring. It has been established that hyperglycemia alters the expression of genes and microRNAs (miRNAs) regulating the fate of neural stem cells (NSCs) during brain development. In this study, the expression of methyl-CpG-binding protein-2 (Mecp2), a global chromatin organizer and a crucial regulator of synaptic proteins, was analyzed in NSCs obtained from the forebrain of embryos of diabetic mice. Mecp2 was significantly downregulated in NSCs derived from embryos of diabetic mice when compared to controls. miRNA target prediction revealed that the miR-26 family could regulate the expression of Mecp2, and further validation confirmed that Mecp2 is a target of miR-26b-5p. Knockdown of Mecp2 or overexpression of miR-26b-5p altered the expression of tau protein and other synaptic proteins, suggesting that miR-26b-5p alters neurite outgrowth and synaptogenesis via Mecp2. This study revealed that maternal diabetes upregulates the expression of miR-26b-5p in NSCs, resulting in downregulation of its target, Mecp2, which in turn perturbs neurite outgrowth and expression of synaptic proteins. Overall, hyperglycemia dysregulates synaptogenesis that may manifest as neurodevelopmental disorders in offspring from diabetic pregnancy.
AB - Maternal diabetes has been associated with a greater risk of neurodevelopmental disorders in offspring. It has been established that hyperglycemia alters the expression of genes and microRNAs (miRNAs) regulating the fate of neural stem cells (NSCs) during brain development. In this study, the expression of methyl-CpG-binding protein-2 (Mecp2), a global chromatin organizer and a crucial regulator of synaptic proteins, was analyzed in NSCs obtained from the forebrain of embryos of diabetic mice. Mecp2 was significantly downregulated in NSCs derived from embryos of diabetic mice when compared to controls. miRNA target prediction revealed that the miR-26 family could regulate the expression of Mecp2, and further validation confirmed that Mecp2 is a target of miR-26b-5p. Knockdown of Mecp2 or overexpression of miR-26b-5p altered the expression of tau protein and other synaptic proteins, suggesting that miR-26b-5p alters neurite outgrowth and synaptogenesis via Mecp2. This study revealed that maternal diabetes upregulates the expression of miR-26b-5p in NSCs, resulting in downregulation of its target, Mecp2, which in turn perturbs neurite outgrowth and expression of synaptic proteins. Overall, hyperglycemia dysregulates synaptogenesis that may manifest as neurodevelopmental disorders in offspring from diabetic pregnancy.
KW - maternal hyperglycemia
KW - microRNA
KW - neurodevelopmental disorders
KW - synapse
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U2 - 10.3390/cells12111516
DO - 10.3390/cells12111516
M3 - Article
C2 - 37296636
AN - SCOPUS:85161383065
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 11
M1 - 1516
ER -
