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Prenatal exposure of human brain to ethanol impairs neuronal migration. The adverse effects of ethanol on brain development may be partly due to the ethanol-induced disturbance of neuronal interaction with laminin, a protein involved in neuronal migration and axon guidance. Integrins are important receptors for neuronal adhesion and migration to laminin during development. We investigated the effects of ethanol exposure on neuronal migration, and integrin-mediated migration toward laminin. Human neuroblastoma cells (SK-N-SH, ATCC) were exposed to ethanol (0.5 mg/ml) or control media for 1 week. Subsequently, migration of an equal number of neuroblastoma cells toward laminin was investigated, and the effect of the neutralizing anti-integrin antibodies, anti-α1, anti-α2, anti-α3, anti-α6, and anti-β1, were compared to IgG. The number of neuroblastoma cells that migrated was counted in a masked fashion. The average of quadruplet wells was taken for each group in each experiment. There were 2-4 experiments for each group. Exposure to ethanol for 1 week resulted in loss of 16 ±4 % of neurons compared to controls (mean±SEM, n=4, p <0.05). Ethanol exposure resulted in 38±9% inhibition of migration of neuroblastoma cells to laminin (n=7, p <0.05). (Table) Integrin α3β1, and to a lesser extent α1β1, mediated laminin-directed migration of SK-N-SH neuroblastoma cells, independent of ethanol exposure. Integrin α6β1 failed to mediate laminin-directed migration in the absence of ethanol; however, in the presence of ethanol, integrin α6β1 mediated in part laminin-directed migration of the neuroblastoma cells. This data suggests that the activity of integrin α6β1 is altered by ethanol exposure, potentially resulting in an altered neuronal migration pattern.
Tan, S., Gladson, C. The Role of Integrin Receptors in Ethanol-Induced Changes in Neuronal Migration.
Pediatr Res45, 75 (1999). https://doi.org/10.1203/00006450-199904020-00447
