Cell population depletion associated with fetal alcohol brain damage: mechanisms of BAC-dependent cell loss.
Neuronal death is one of the most serious consequences of alcohol exposure during development. Studies described in this paper used a neonatal rat model to address factors affecting neuronal death following alcohol exposure during the period of rapid brain growth, and relate them to possible mechanisms of damage. The profile of blood alcohol concentrations (BACs) is an important variable influencing both brain growth deficits and neuronal death--a smaller daily dose of alcohol can be more damaging than a larger daily dose, if it is consumed in a binge-like pattern that produces relatively higher BACs. Alcohol exposure for a single day also can be damaging, producing both brain growth deficits and neuron loss, if high BACs are obtained. Various brain regions and different neuronal populations within a given brain area exhibit different degrees of vulnerability. Some neuronal loss clearly is a function of cell death due to direct effects of alcohol, while other deficits may be due to either primary or secondary effects of the alcohol insult. In the cerebellum, a maturational or metabolic factor also appears to be involved with alcohol-induced neuronal death. Immunocytochemical studies using a monoclonal antibody against microtubule-associated protein 2 (MAP2) indicated that cerebellar lobules containing Purkinje cells that are in the process of extending dendrites are ones that are more vulnerable to alcohol than lobules containing Purkinje cells that mature later. Alcohol exposure during brain development may be producing neuron attrition in multiple ways, including disruption of membrane integrity, inhibition of protein synthesis or other alterations such as lipid solubility, or by disruption of cytoskeletal elements.
West
J R
JR
Department of Anatomy, College of Medicine, University of Iowa, Iowa City 52242.
Goodlett
C R
CR
Bonthius
D J
DJ
Hamre
K M
KM
Marcussen
B L
BL
D000818:Animals; D001925:Brain Damage, Chronic / Q000097:blood / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000097:blood / Q000473:pathology*; D006801:Humans; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy
D000431:Ethanol