TY - JOUR
T1 - Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats
AU - Valle-Bautista, Rocío
AU - Márquez-Valadez, Berenice
AU - Fragoso-Cabrera, América D.
AU - García-López, Guadalupe
AU - Díaz, Néstor Fabián
AU - Herrera-López, Gabriel
AU - Griego, Ernesto
AU - Galván, Emilio J.
AU - Arias-Montaño, José Antonio
AU - Molina-Hernández, Anayansi
N1 - Funding 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.
Publisher Copyright:
© Copyright © 2020 Valle-Bautista, Márquez-Valadez, Fragoso-Cabrera, García-López, Díaz, Herrera-López, Griego, Galván, Arias-Montaño and Molina-Hernández.
PY - 2020/9/16
Y1 - 2020/9/16
N2 - 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.
AB - 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.
KW - cerebral cortex development
KW - maternal diabetes
KW - neocortical cytoarchitecture
KW - neocortical function
KW - primary motor cortex
UR - http://www.scopus.com/inward/record.url?scp=85091932169&partnerID=8YFLogxK
U2 - 10.3389/fcell.2020.564561
DO - 10.3389/fcell.2020.564561
M3 - Article
AN - SCOPUS:85091932169
SN - 2296-634X
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 564561
ER -