Ethanol effects on cerebellar myelination in a postnatal mouse model of fetal alcohol spectrum disorders

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2021-11, Vol.96, p.43-53
• Main Authors: Niedzwiedz-Massey, Victoria M., Douglas, James C., Rafferty, Tonya, Kane, Cynthia J.M., Drew, Paul D.
• Format: Article
• Language: English
• Subjects: Alcohol use; Animal cognition; Cerebellum; Cognitive ability; Ethanol; FASD; Fetal alcohol syndrome; Gene expression; Glial stem cells; Laboratory animals; Maturation; myelin; Myelination; Neonates; Neuropathology; oligodendrocyte; oligodendrocyte differentiation; Oligodendrocytes; Optic nerve; Statistical analysis; Toxicity
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2021.07.003

Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there are no effective treatments for these disorders. Cerebellar neuropathology is common in FASD and can cause impaired cognitive and motor function. The current study evaluates the effects of ethanol on oligodendrocyte-lineage cells, as well as molecules that modulate oligodendrocyte differentiation and function in the cerebellum in a postnatal mouse model of FASD. Neonatal mice were treated with ethanol from P4–P9 (postnatal day), the cerebellum was isolated at P10, and mRNAs encoding oligodendrocyte-associated molecules were quantitated by qRT-PCR. Our studies demonstrated that ethanol significantly reduced the expression of markers for multiple stages of oligodendrocyte maturation, including oligodendrocyte precursor cells, pre-myelinating oligodendrocytes, and mature myelinating oligodendrocytes. Additionally, we determined that ethanol significantly decreased the expression of molecules that play critical roles in oligodendrocyte differentiation. Interestingly, we also observed that ethanol significantly reduced the expression of myelin-associated inhibitors, which may act as a compensatory mechanism to ethanol toxicity. Furthermore, we demonstrate that ethanol alters the expression of a variety of molecules important in oligodendrocyte function and myelination. Collectively, our studies increase our understanding of specific mechanisms by which ethanol modulates myelination in the developing cerebellum, and potentially identify novel targets for FASD therapy. [Display omitted] •Ethanol alters gene expression in the cerebellum in a postnatal model of FASD.•Ethanol reduces stage-specific oligodendrocyte-lineage cell markers.•Ethanol reduces expression of molecules critical to oligodendrocyte differentiation.•Ethanol alters expression of molecules important for oligodendrocyte function/myelination.•The current studies define mechanisms by which ethanol reduces myelination.