Recent breakthroughs in understanding the cerebellum's role in fetal alcohol spectrum disorder: A systematic review

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2024-09, Vol.119, p.37-71
• Main Authors: Leung, Eric C.H., Jain, Priyanka, Michealson, Marisa A., Choi, Hyesun, Ellsworth-Kopkowski, Alexis, Valenzuela, C. Fernando
• Format: Article
• Language: English
• Subjects: Animal models; Brain research; Cerebellum; Cognitive ability; development; Ethanol; fetal; Fetal alcohol syndrome; Kinases; Motor ability; Neurodevelopmental disorders; Neurons; Ostomy; prenatal; Prenatal experience; Protein structure; Reviews; Structure-function relationships; Systematic review; Therapeutic applications
• ISSN: 0741-8329; 1873-6823; 1873-6823
• DOI: 10.1016/j.alcohol.2023.12.003

Exposure to alcohol during fetal development can lead to structural and functional abnormalities in the cerebellum, a brain region responsible for motor coordination, balance, and specific cognitive functions. In this systematic review, we comprehensively analyze a vast body of research conducted on vertebrate animals and humans over the past 13 years. We identified studies through PubMed and screened them following PRISMA guidelines. Data extraction and quality analysis were conducted using Covidence systematic review software. A total of 108 studies met our inclusion criteria, with the majority (79 studies) involving vertebrate animal models and 29 studies focusing on human subjects. Animal models included zebrafish, mice, rats, sheep, and non-human primates, investigating the impact of ethanol on cerebellar structure, gene/protein expression, physiology, and cerebellar-dependent behaviors. Additionally, some animal studies explored potential therapeutic interventions against ethanol-induced cerebellar damage. The human studies predominantly adopted cohort designs, exploring the effects of prenatal alcohol exposure on cerebellar structure and function. Certain human studies delved into innovative cerebellar-based diagnostic approaches for fetal alcohol spectrum disorder (FASD). The collective findings from these studies clearly indicate that the cerebellum is involved in various neurophysiological deficits associated with FASD, emphasizing the importance of evaluating both cerebellar structure and function in the diagnostic process for this condition. Moreover, this review sheds light into potential therapeutic strategies that can mitigate prenatal alcohol exposure-induced cerebellar damage. •The cerebellum is an important target of prenatal ethanol exposure.•We systematically analyzed animal and human research in this area.•PRISM guidelines for systematic review were followed.•A total of 79 animal studies and 29 human studies met inclusion criteria.•Cerebellar dysfunction contributes to many prenatal ethanol-induced neurophysiological deficits.