Hyland N P, O'Mahony S M, O'Malley D, O'Mahony C M, Dinan T G, Cryan J F
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.
Neurogastroenterol Motil. 2015 Jan;27(1):105-13. doi: 10.1111/nmo.12486. Epub 2014 Dec 2.
Early-life stress and a genetic predisposition to display an anxiety- and depressive-like phenotype are associated with behavioral and gastrointestinal (GI) dysfunction. Animals exposed to early-life stress, and those genetically predisposed to display anxiety or depressive behaviors, have proven useful tools in which to study stress-related GI disorders, such as irritable bowel syndrome (IBS). IBS is a heterogeneous disorder, and likely a consequence of both genetic and environmental factors. However, the combined effects of early-life stress and a genetic predisposition to display anxiety- and depression-like behaviors on GI function have not been investigated.
We assessed the effect of maternal separation (MS) on behavioral and GI responses in WKY animals relative to a normo-anxious reference strain.
Both non-separated (NS) WKY and WKY-MS animals displayed anxiety-like responses in the open-field test and depressive-like behaviors in the forced swim test relative to Sprague-Dawley rats. However, MS had no further influence on anxiety- and depressive-like behaviors exhibited by this stress-prone rat strain. Similarly, corticosterone levels measured after the OFT were insensitive to MS in WKY animals. However, WKY-MS displayed significantly increased colonic visceral hypersensitivity, fecal output, and altered colonic cholinergic sensitivity.
CONCLUSIONS & INFERENCES: Our data suggest that early-life stress, on the background of a genetic predisposition to display an anxiety- and depressive-like phenotype, selectively influences GI function rather than stress-related behaviors. Thus, our findings highlight the importance of genetic predisposition on the outcome of early-life adversity on GI function.
早年生活应激以及表现出焦虑和抑郁样表型的遗传易感性与行为和胃肠道（GI）功能障碍有关。已证明，暴露于早年生活应激的动物以及那些具有表现出焦虑或抑郁行为遗传倾向的动物，是研究应激相关胃肠道疾病（如肠易激综合征（IBS））的有用工具。IBS是一种异质性疾病，可能是遗传和环境因素共同作用的结果。然而，早年生活应激和表现出焦虑和抑郁样行为的遗传易感性对胃肠道功能的综合影响尚未得到研究。
我们评估了母体分离（MS）对WKY动物相对于正常焦虑对照品系的行为和胃肠道反应的影响。
相对于Sprague-Dawley大鼠，未分离（NS）的WKY和WKY-MS动物在旷场试验中均表现出焦虑样反应，在强迫游泳试验中表现出抑郁样行为。然而，MS对这种易应激大鼠品系表现出的焦虑和抑郁样行为没有进一步影响。同样，在旷场试验后测量的皮质酮水平对WKY动物的MS不敏感。然而，WKY-MS表现出结肠内脏超敏反应显著增加、粪便排出量增加以及结肠胆碱能敏感性改变。
我们的数据表明，在具有表现出焦虑和抑郁样表型遗传易感性的背景下，早年生活应激选择性地影响胃肠道功能而非应激相关行为。因此，我们的研究结果突出了遗传易感性对早年生活逆境对胃肠道功能影响结果的重要性。
