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Maternal hyperglycemia disturbs neocortical neurogenesis via epigenetic regulation in C57BL/6J mice.
- Source :
-
Cell death & disease [Cell Death Dis] 2019 Mar 01; Vol. 10 (3), pp. 211. Date of Electronic Publication: 2019 Mar 01. - Publication Year :
- 2019
-
Abstract
- Offspring of mothers with hyperglycemia during pregnancy have a higher incidence of long-term neuropsychiatric disorders than offspring from a normal pregnancy, indicating that neocortical neurogenesis might be affected by maternal hyperglycemia. A paucity of study evaluating the effects of hyperglycemia on neocortical neurogenetic differentiation of neural stem cells, and the mechanism remains unclear. We sought to investigate the the roles and possible molecular mechanism of maternal hyperglycemia on neocortical neurogenetic differentiation of neural stem cells. We established a mouse model of a hyperglycemic pregnancy to study effects of intrauterine exposure to maternal hyperglycemia on neocortical neurogenesis. We observed morphological changes in the neocortex and detected the neurogenetic differentiation of neural stem cells in offspring affected by high glucose levels. We investigated the regulatory network between epigenetic modification and transcription factors in differentiated neural stem cells under hyperglycemic conditions. Maternal hyperglycemia disturbs neocortical lamination in some non-malformed offspring. Our results suggested that hyperglycemia altered the early-born neuron fate and the distribution of newborn neurons in deep layers by promoting the earlier differentiation of neural stem cells. Altered histone acetylation and its regulation on the transcription of proneural genes might be correlated to the disrupted differentiation of neural stem cells and altered distribution of newborn projection neurons in the neocortex. Our data raised the possibility that maternal hyperglycemia in pregnancy disturbs the laminar distribution of neocortical projection neurons in some non-malformed offspring via epigenetic regulation on neural stem cell differentiation and the birthdate of neocortical neurons.
- Subjects :
- Acetylation
Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Cell Differentiation physiology
Disease Models, Animal
Female
Gene Expression Regulation, Developmental
Histone Acetyltransferases genetics
Histone Acetyltransferases metabolism
Histone Deacetylase 1 genetics
Histone Deacetylase 1 metabolism
Histones chemistry
Histones metabolism
Mice
Mice, Inbred C57BL
Neocortex growth & development
Neocortex metabolism
Nerve Tissue Proteins metabolism
Neural Stem Cells cytology
Neural Stem Cells ultrastructure
Neural Tube Defects pathology
Neurons cytology
Pregnancy
Epigenesis, Genetic
Hyperglycemia
Neural Stem Cells metabolism
Neurogenesis physiology
Neurons metabolism
Pregnancy Complications
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 30824686
- Full Text :
- https://doi.org/10.1038/s41419-019-1438-z