Breivik Torbjørn, Gundersen Yngvar, Murison Robert, Turner Jonathan D, Muller Claude P, Gjermo Per, Opstad Kristian
Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway ; Norwegian Defence Research Establishment, Division for Protection, Kjeller, Norway.
Norwegian Defence Research Establishment, Division for Protection, Kjeller, Norway.
Open Dent J. 2015 Jan 30;9:65-78. doi: 10.2174/1874210601509010065. eCollection 2015.
Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood.
Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response.
Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone.
Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.
早年不良事件可能通过永久性失调大脑控制的免疫调节系统，影响个体成年后对慢性炎症性疾病的易感性/抵抗力。我们研究了出生后早期母婴分离对成年期实验性牙周炎严重程度以及全身应激和免疫反应的影响。
将对牙周炎有抵抗力的Lewis大鼠幼崽在出生后第2 - 14天每天与母亲分离3小时（称为母婴剥夺；MD），在同一时期每天分离15分钟（称为抚摸；HD），或不做处理。成年后，在新的应激环境中测试它们的行为，并施加结扎诱导的牙周炎21天。在处死前2小时，所有大鼠接受革兰氏阴性菌脂多糖（LPS）刺激以诱导强烈的免疫和应激反应。
与未受干扰的对照组相比，MD组大鼠成年后发生的牙周骨丧失明显更多，而HD组大鼠的疾病程度有减轻趋势。MD组和HD组大鼠在新的旷场试验中表现出类似抑郁的行为，而MD组大鼠海马体中糖皮质激素受体（Gr）表达较高，HD组大鼠海马体Gr表达相关基因的甲基化发生改变。LPS刺激后，MD组和HD组大鼠循环中细胞因子TGF - 1β水平的升高明显较低，但应激激素皮质酮水平无显著差异。
生命早期的应激性环境暴露可能以影响对牙周炎易感性/抵抗力的方式改变免疫反应。
