Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development
Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains un...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00237/full |
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| author | Seshadri Ramya Sukanya Shyamasundar Boon Huat Bay S. Thameem Dheen |
| author_facet | Seshadri Ramya Sukanya Shyamasundar Boon Huat Bay S. Thameem Dheen |
| author_sort | Seshadri Ramya |
| collection | DOAJ |
| description | Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis. To address this, high throughput miRNA expression profiling in neural stem cells (NSCs) isolated from the forebrain of embryos from normal or streptozotocin-induced diabetic pregnancy was carried out. It is known that maternal diabetes results in fetal hypoglycemia/hyperglycemia or hypoxia. Hence, NSCs from embryos of control pregnant mice were exposed to low or high glucose or hypoxia in vitro. miRNA pathway analysis revealed distinct deregulation of several biological pathways, including axon guidance pathway, which are critical for brain development in NSCs exposed to different treatments. Among the differentially expressed miRNAs, the miRNA-30 family members which are predicted to target genes involved in brain development was upregulated in NSCs from embryos of diabetic pregnancy when compared to control. miRNA-30b was found to be upregulated while its target gene Sirtuin 1 (Sirt1), as revealed by luciferase assay, was down regulated in NSCs from embryos of diabetic pregnancy. Further, overexpression of miRNA-30b in NSCs, resulted in decreased expression of Sirt1 protein, and altered the neuron/glia ratio. On the other hand, siRNA mediated knockdown of Sirt1 in NSCs promoted astrogenesis, indicating that miRNA-30b alters lineage specification via Sirt1. Overall, these results suggest that maternal diabetes alters the genes involved in neural tube formation via regulating miRNAs. |
| first_indexed | 2024-12-12T08:09:18Z |
| format | Article |
| id | doaj.art-987a2d28f8f844bba76ba6d683450dcc |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-12T08:09:18Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-987a2d28f8f844bba76ba6d683450dcc2022-12-22T00:31:50ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-07-011010.3389/fnmol.2017.00237270766Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube DevelopmentSeshadri RamyaSukanya ShyamasundarBoon Huat BayS. Thameem DheenMaternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis. To address this, high throughput miRNA expression profiling in neural stem cells (NSCs) isolated from the forebrain of embryos from normal or streptozotocin-induced diabetic pregnancy was carried out. It is known that maternal diabetes results in fetal hypoglycemia/hyperglycemia or hypoxia. Hence, NSCs from embryos of control pregnant mice were exposed to low or high glucose or hypoxia in vitro. miRNA pathway analysis revealed distinct deregulation of several biological pathways, including axon guidance pathway, which are critical for brain development in NSCs exposed to different treatments. Among the differentially expressed miRNAs, the miRNA-30 family members which are predicted to target genes involved in brain development was upregulated in NSCs from embryos of diabetic pregnancy when compared to control. miRNA-30b was found to be upregulated while its target gene Sirtuin 1 (Sirt1), as revealed by luciferase assay, was down regulated in NSCs from embryos of diabetic pregnancy. Further, overexpression of miRNA-30b in NSCs, resulted in decreased expression of Sirt1 protein, and altered the neuron/glia ratio. On the other hand, siRNA mediated knockdown of Sirt1 in NSCs promoted astrogenesis, indicating that miRNA-30b alters lineage specification via Sirt1. Overall, these results suggest that maternal diabetes alters the genes involved in neural tube formation via regulating miRNAs.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00237/fullneural tube defectsneural stem cellshyperglycemiahypoglycemiahypoxiamicroRNA |
| spellingShingle | Seshadri Ramya Sukanya Shyamasundar Boon Huat Bay S. Thameem Dheen Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development Frontiers in Molecular Neuroscience neural tube defects neural stem cells hyperglycemia hypoglycemia hypoxia microRNA |
| title | Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development |
| title_full | Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development |
| title_fullStr | Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development |
| title_full_unstemmed | Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development |
| title_short | Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development |
| title_sort | maternal diabetes alters expression of micrornas that regulate genes critical for neural tube development |
| topic | neural tube defects neural stem cells hyperglycemia hypoglycemia hypoxia microRNA |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00237/full |
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