Long-term modulations in the vertebral transcriptome of adolescent-stage rats exposed to binge alcohol.
OBJECTIVE
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.
Callaci
John J
JJ
Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA. jcallaci@lumc.edu
Himes
Ryan
R
Lauing
Kristen
K
Roper
Phillip
P
D000375:Aging; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking; D000435:Alcoholic Intoxication / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D013695:Temperance
D000431:Ethanol; D000426:Alcohol Dehydrogenase