The effects of alcohol exposure on cortical neuron differentiation and nerve growth factor.

摘要

A significant cause of numerous neurodevelopmental problems manifested during early childhood is attributed to abnormalities in cortical development (Swayze, et al., 1997). Prenatal alcohol exposure can cause profound abnormalities in the organization and the ontogeny of neurons that comprise the cerebral cortex (Clarren, Alvord et al., 1978, Ferrer & Galofre, 1987. The developmental neurotoxicity of alcohol within the cerebral cortex may be mediated by alterations in the level of neurotrophic factors such as Nerve Growth Factor (NGF). The reduction of NGF production and/or availability during development may account for various abnormalities in neuron generation, proliferation, differentiation and migration within the cerebral cortex (Miller, 1986, 1988, 1993). Alteration in cortical development may account for cognitive and learning disabilities following prenatal alcohol exposure. The dose and duration of alcohol exposure are important factors in determining the type and severity of brain damage. In the present project, human cortical neurons (HCN-1A) were assessed for the temporal (0 to 72 hours) and the concentration-dependent effects of alcohol (0, 0.15, 0.30, 0.60, 1.2, 1.8, 2.4g/dl) on morphological differentiation (neurite processes and branching). The ameliorative effects of supplemental NGF on the alcohol-induced inhibition of neuronal outgrowth was also assessed. The effects of alcohol exposure at various time intervals (0 to 24 hours) on NGF transcription were determined using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR).; The results supported the hypothesis that alcohol exposure produced concentration-dependent decreases in neuronal differentiation and decreases in differentiation maybe due in part to alterations in NGF mRNA transcription. Supplemental NGF was able to ameliorate alcohol-induced decreases in neuronal processes and branching processes. The result of this study may provide insight and direction into methods of ameliorating alcohol-induced brain abnormalities.