Development Deficiency of Oligodendrocyte and Myelination in the Central Nervous System of the Fetal Alcohol Syndrome Mouse Model

Abstract

Fetal alcohol spectrum disorder (FASD) is a severe condition characterized by physical and neurodevelopmental abnormalities in the fetus resulting from prenatal alcohol exposure (PAE). Behavioral abnormalities associated with white matter damage have been extensively investigated in FASD patients and animal models, which suggested the involvement of myelination in the FASD pathology. However, the impact of FASD on oligodendrocytes (OLs) and myelination within the central nervous system (CNS) and the underlying mechanisms are little discovered. Here, we showed impaired myelination in the CNS of the male FASD mouse model, which is associated with hyperactivity-like behaviors, whereas the female FASD mice exhibit delayed myelin formation and normal behaviors. Furthermore, myelination deficiency in FASD is due to the inhibition of oligodendrocyte precursors (OPCs) proliferation. Additionally, FASD exerts an impact on the quantity and differentiation of redial glia cells (RGCs), which may contribute to the defect of oligodendrocytes development and myelination. Together, our data reveals the deficiency of oligodendrocyte development and myelination in the CNS of the FASD mouse model and the possible underlying mechanism, suggesting a potential therapy target for FASD.

Note:
Funding declaration: This work was supported by National Natural Science Foundation of China (82060224), Scientific Project of Guizhou Province (Qian Comprehensive Basic Science [2020]1Y088, [2017]5733-066, [2020]-002), and PhD research startup foundation of Zunyi medical University (F-958).

Conflict of Interests: The authors claim no conflicts of interest.

Ethical Approval: This study was approved by the Animal Experimental Ethics Committee of Zunyi Medical University, and all animals met the ethical requirements.

Keywords: Fetal Alcohol Syndrome, Prenatal alcohol exposure, myelination, oligodendrocytes, Redial Glia Cells