Migration of cortical neurons is altered by gestational exposure to ethanol.
Rats prenatally exposed to ethanol exhibit a variety of structural anomalies in the central nervous system. One of the key features of experimental fetal alcohol syndrome is microencephaly. Cerebral cortex is particularly susceptible to the effects of prenatal exposure to ethanol. Its total mass is reduced, it is thinner, and it contains fewer neurons and glia. Various studies in rats and humans suggest that chronic early exposure to ethanol leads to a massive reorganization of cortex characterized by heterotopic clusters of neurons. A pulse and chase study with [3H]thymidine autoradiography was used to determine if gestational exposure to ethanol leads to defects in neuronal migration. Rats were fed an ethanol-containing diet between gestational day (G) 6 and G21, pair-fed a liquid control diet, or fed chow. Ethanol delayed the migration of early-generated neurons (those born on G13) to deep cortex by 2 days. Moreover, the migration of late-generated neurons (those born on G21) was delayed 4 to 6 days by ethanol, and often these neurons terminated their migration in ectopic locations. Ethanol significantly decreased the rate of migration and the time postmitotic cells remained in the proliferative zones. On the other hand, ethanol did not have a significant effect on the rate of cortical expansion and the fraction of cells that left the proliferating population in order to migrate to cortex. Thus, the migration of young neurons was profoundly altered by prenatal exposure to ethanol. Such delays may lead to a desynchronization of cortical development that makes it impossible for cortical neurons to establish a normal circuitry.
Miller
M W
MW
Research Service, Veterans Affairs Medical Center, Iowa City, Iowa.
D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000196:embryology* / Q000473:pathology; D005865:Gestational Age; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D051381:Rats