Long-Term Modulations in the Vertebral Transcriptome of Adolescent-Stage Rats Exposed to Binge Alcohol
Long-Term Modulations in the Vertebral Transcriptome of Adolescent-Stage Rats Exposed to Binge Alcohol
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DOI：
10.1093/alcalc/agq030
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发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Roper, Phillip
中科院分区：
文献类型：
--
作者：
Callaci, John J.;Himes, Ryan;Roper, Phillip
目的：危险的饮酒行为在青少年中很常见，但人们对他们达到峰值骨量和长期骨骼完整性的后果知之甚少。我们以前证明，酗酒暴露的青春期大鼠表现出特定部位的骨密度和骨强度的减少，这是不完全恢复后，长期戒酒。目前，我们分析了酒精治疗和戒酒后青少年大鼠的脊椎转录组，以确定腰椎的长期分子变化。方法：将60只雄性青春期Sprague-Dawley大鼠分配到6个治疗组之一，接受酗酒（3 g/kg）或生理盐水腹腔注射，连续3天（急性暴食）、连续4个每周（3天）一次的暴食周期（慢性暴食）或4个每周一次的暴食周期，随后是30天的戒断期（慢性暴食伴戒断）。治疗后，使用基因阵列技术测定腰椎的整体转录变化。结果如下：对青春期大鼠脊椎转录组的分析确定了酗酒敏感基因簇，这些基因在骨损伤之前就显示出差异表达模式，并在酒精治疗停止后持续存在。这些基因簇的功能分组确定了急性和慢性暴食治疗后受影响的候选细胞通路，以及禁欲后仍受调节的通路。结论：这些结果表明，酗酒暴露可以产生破坏正常的骨基因表达模式的青春期大鼠，持续远远超过活跃中毒期间。这些数据可能与反复酗酒的青少年达到峰值骨量和未来患骨骼疾病的风险有关。
Aims: Dangerous alcohol consumption practices are common in adolescents, yet little is known about their consequences on attainment of peak bone mass and long-term skeletal integrity. We previously demonstrated that binge alcohol-exposed adolescent rats showed site-specific reductions in accruement of bone mineral density and bone strength, which were incompletely recovered following prolonged alcohol abstinence. Currently, we analysed the vertebral transcriptome of adolescent rats following alcohol treatment and abstinence to identify long-term molecular changes in the lumbar spine. Methods: Sixty male adolescent Sprague-Dawley rats were assigned to one of six treatment groups receiving binge alcohol (3 g/kg) or saline i.p., 3 consecutive days (acute binge), 4 consecutive weekly (3-day) binge cycles (chronic binge) or 4 weekly binge cycles followed by a 30-day abstinence period (chronic binge with abstinence). Following treatment, lumbar vertebrae were assayed for global transcriptional changes using gene array technology. Results: Analysis of the adolescent rat vertebral transcriptome identified clusters of binge alcohol-sensitive genes displaying differential expression patterns starting before bone damage was seen and persisting after alcohol treatment was discontinued. Functional grouping of these gene clusters identified candidate cellular pathways affected following acute and chronic binge treatment, as well as pathways remaining modulated following abstinence. Conclusions: These results demonstrate that binge alcohol exposure can produce disruptions of normal bone gene expression patterns in the adolescent rat that persist well beyond the period of active intoxication. This data may have relevance to peak bone mass attainment and future risk of skeletal disease in adolescents engaging in repeated binge-drinking episodes.