Parks Elizabeth A, McMechan Andrew P, Hannigan John H, Berman Robert F
Department of Neurological Surgery, University of California, Davis, California 95616, USA.
Alcohol Clin Exp Res. 2008 Oct;32(10):1741-51. doi: 10.1111/j.1530-0277.2008.00759.x. Epub 2008 Jul 24.
Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats.
Pregnant rats received alcohol by gavage, 0, 4, or 6 g/kg/d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis.
Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions.
Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats.
孕期酒精暴露会导致大脑发育异常，引发行为缺陷，其中一些缺陷可通过环境富集得到改善。由于环境富集和孕期酒精暴露均可单独改变神经营养因子的表达，我们研究了孕期酒精与断奶后环境富集对大鼠脑神经营养因子水平的相互作用。
怀孕大鼠在妊娠第8至20天通过灌胃给予酒精，剂量分别为0、4或6 g/kg/天（零剂量、低剂量或高剂量组），或不进行处理（未处理组）。产后第21天断奶后，将子代分别饲养在隔离、群居或丰富环境中6周。然后测量额叶皮质、枕叶皮质、海马体和小脑蚓部中神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）的水平。
孕期酒精暴露使额叶皮质（高剂量组）和小脑蚓部（高剂量和低剂量组）中的NGF水平升高；使额叶皮质、枕叶皮质和海马体中的BDNF水平升高（低剂量组），并使海马体和小脑蚓部中的NT-3水平升高（高剂量组）。环境富集导致枕叶皮质中的NGF、BDNF和NT-3水平降低，额叶皮质中的NGF水平降低。孕期酒精处理与环境之间唯一显著的相互作用发生在小脑蚓部，孕期酒精暴露后，饲养在丰富环境中的动物NT-3水平较高，但饲养在隔离或群居条件下的动物则不然。
孕期酒精暴露和断奶后的饲养条件均会改变脑神经营养因子水平，但这些影响似乎在很大程度上是独立的。尽管环境富集可改善功能结局，但这些结果并未为在复杂环境中饲养可改善孕期酒精对大鼠脑神经营养因子水平影响这一假说提供有力支持。
