Maternal diabetes has been related to low verbal task scores, impaired fine and gross motor skills, and poor performance in graphic and visuospatial tasks during childhood. The primary motor cortex is important for controlling motor functions, and embryos exposed to high glucose show changes in cell proliferation, migration, and differentiation during corticogenesis. However, the existing studies do not discriminate between embryos with or without neural tube defects, making it difficult to conclude whether the reported changes are related to neural tube defects or other anomalies. Furthermore, postnatal effects on central nervous system cytoarchitecture and function have been scarcely addressed. Through molecular, biochemical, morphological, and electrophysiological approaches, we provide evidence of impaired primary motor cerebral cortex lamination and neuronal function in pups from diabetic rats, showing an altered distribution of SATB2, FOXP2, and TBR1, impaired cell migration and polarity, and decreased excitability of deep-layer cortical neurons, suggesting abnormalities in cortico-cortical and extra-cortical innervation. Furthermore, phase-plot analysis of action potentials suggests changes in the activity of potassium channels. These results indicate that high-glucose insult during development promotes complex changes in migration, neurogenesis, cell polarity establishment, and dendritic arborization, which in turn lead to reduced excitability of deep-layer cortical neurons.
Bibliographical noteFunding Information:
We acknowledge funding by INPer and CONACyT to AM-H and CONACyT fellowship to RV-B (576845). We thank Talía Estrada Rojas (INPer) for assisting with animal care. Funding. This study was funded by INPer federal grants (3230-21202-01-2015) and CONACyT (CB-2015-254847) to AM-H and CONACyT CB-2016-281617 to EJG.
© Copyright © 2020 Valle-Bautista, Márquez-Valadez, Fragoso-Cabrera, García-López, Díaz, Herrera-López, Griego, Galván, Arias-Montaño and Molina-Hernández.
- cerebral cortex development
- maternal diabetes
- neocortical cytoarchitecture
- neocortical function
- primary motor cortex
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology