Prenatal ethanol exposure impairs the formation of radial glial fibers and promotes the transformation of GFAPδ-positive radial glial cells into astrocytes

During embryonic cortical development, radial glial cells (RGCs) are the major source of neurons, and these also serve as a supportive scaffold to guide neuronal migration. Similar to Vimentin, glial fibrillary acidic protein (GFAP) is one of the major intermediate filament proteins present in glial cells. Previous studies confirmed that prenatal ethanol exposure (PEE) significantly affected the levels of GFAP and increased the disassembly of radial glial fibers. GFAP delta is a variant of GFAP that is specifically expressed in RGCs; however, to the best of our knowledge, there are no reports regarding how PEE influences its expression during cortical development. In the present study, the effects of PEE on the expression and distribution of GFAP delta during early cortical development were assessed. It was found that PEE significantly decreased the expression levels of GFAP and GFAP delta. Using double immunostaining, GFAP delta was identified to be specifically expressed in apical and basal RGCs, and was co-localized with other intermediate filament proteins, such as GFAP, Nestin and Vimentin. Additionally, PEE significantly affected the morphology of radial glial fibers and altered the behavior of RGCs. The loss of GFAP delta accelerated the transformation of RGCs into astrocytes. Using co-immunostaining with Ki67 or phospho-histone H3, GFAP delta(+) cells were observed to be proliferative or mitotic cells, and ethanol treatment significantly decreased the proliferative or mitotic activities of GFAP delta(+) RGCs. Taken together, the results suggested that PEE altered the expression patterns of GFAP delta and impaired the development of radial glial fibers and RGC behavior. The results of the present study provided evidence that GFAP delta may be a promising target to rescue the damage induced by PEE.

Automated summary

PEE significantly decreased the expression levels of GFAP and GFAP delta, affecting the morphology of radial glial fibers and behavior of RGCs. The loss of GFAP delta accelerated the transformation of RGCs into astrocytes, and ethanol treatment decreased the proliferative or mitotic activities of GFAP delta(+) RGCs. These results suggest that GFAP delta may be a promising target to mitigate the damage caused by PEE.