Focus on Apoptosis to Decipher How Alcohol and Many Other Drugs Disrupt Brain Development

Frontiers in Pediatrics

John W. Olney¹ 

关键词: apoptosis;    developing brain;    neurons;    oligodendrocytes;    alcohol;    sedatives;    anesthetics;    anti-epileptics;   

DOI  :  10.3389/fped.2014.00081

学科分类：儿科学

来源: Frontiers

【 摘 要 】

Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed fetal alcohol spectrum disorder (FASD), which may include craniofacial malformations, gross structural brain pathology, and a variety of long-term neuropsychiatric disturbances, or it may consist of subtle brain changes and neuropsychiatric disturbances in the relative absence of gross dysmorphogenic features. Based on a large body of recent evidence, we have proposed (1) that most, if not all, of the deleterious effects of alcohol on the developing brain can be explained by a single mechanism. Alcohol has apoptogenic properties that cause large numbers of CNS progenitor cells, or fully differentiated brain cells (depending on developmental age at time of alcohol exposure) to commit suicide and be deleted from the pool of cells that would ordinarily survive and contribute to the normal functions of the brain. If excessive cell suicide is triggered by alcohol in a very early stage of development, the result, as Sulik and colleagues have shown (2), will be gross dysmorphogenic anomalies (e.g., craniofacial and midline brain anomalies), because the cells deleted are progenitor cells that are responsible for generating cell populations that comprise the building blocks of these craniofacial and brain structures. But if, as we have demonstrated (3–5), alcohol triggers suicide of CNS cells in later stages of development after these cells are already differentiating into neurons and glia, the result will be a reduced number of brain cells, derangement of brain circuitry, and various neuropsychiatric disturbances, depending on which populations of cells have been deleted and what combination of synaptic connections have been disrupted or destroyed.

【 授权许可】

CC BY