Barrera-Bugueño Camila, Realini Ornella, Escobar-Luna Jorge, Sotomayor-Zárate Ramón, Gotteland Martin, Julio-Pieper Marcela, Bravo Javier A
Grupo de NeuroGastroBioquímica, Laboratorio de Química Biológica & Bioquímica de Sistemas, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
Neuroscience. 2017 Sep 17;359:18-29. doi: 10.1016/j.neuroscience.2017.06.064. Epub 2017 Jul 8.
Gut microbiota interventions, including probiotic and prebiotic use can alter behavior in adult animals and healthy volunteers. However, little is known about their effects in younger individuals. To investigate this, male Sprague-Dawley rats (post-natal day 21, PND21) received Lactobacillus casei 54-2-33 (10cfu/ml), inulin as prebiotic (16mg/ml), or both together (synbiotic) via drinking water for 14days. Control rats received water alone. Open field (OF) and elevated plus maze (EPM) behaviors were evaluated at PND34 and 35, respectively. 30min after EPM, brains and trunk blood were collected to evaluate hippocampal 5-HT (mRNA and protein) and plasma corticosterone (CORT). Lactobacillus, inulin and synbiotic-treated rats had fewer entries to the OF's center and spent more time in its periphery than controls. Synbiotic-fed rats explored the EPM's open arms longer than probiotic and inulin-fed rats. Synbiotic, but not Lactobacillus nor inulin-fed rats had lower levels of EPM-evoked CORT than controls. Basal CORT levels, evaluated in a naïve cohort, were higher in Lactobacillus- and inulin-fed rats than controls. In naïve synbiotic-fed rats, 5-HT mRNA levels were higher in dentate gyrus and cornus ammonis 1 layer (CA1), than in all other naïve groups, while hippocampal 5-HT protein levels were lower in bacteria-fed rats than controls. 5-HT mRNA changes suggest complex effects of gut microbes on hippocampal gene expression machinery, probably involving endogenous/exogenous bacteria and prebiotics interactions. Importantly, age might also influence their behavioral outcomes. Together, these data suggest that interventions in young rat microbiota evoke early behavioral changes upon stress, apparently in a hypothalamus-pituitary-adrenal axis independent fashion.
肠道微生物群干预措施，包括使用益生菌和益生元，可以改变成年动物和健康志愿者的行为。然而，它们对较年轻个体的影响却鲜为人知。为了对此进行研究，雄性斯普拉格-道利大鼠（出生后第21天，即PND21）通过饮用水接受干酪乳杆菌54-2-33（10cfu/ml）、作为益生元的菊粉（16mg/ml）或两者一起（合生元），持续14天。对照大鼠只接受水。分别在PND34和35评估旷场（OF）和高架十字迷宫（EPM）行为。在EPM测试后30分钟，采集大脑和躯干血液以评估海马体5-羟色胺（mRNA和蛋白质）以及血浆皮质酮（CORT）。与对照组相比，接受乳酸杆菌、菊粉和合生元治疗的大鼠进入OF中心的次数更少，在其周边花费的时间更多。食用合生元的大鼠探索EPM开放臂的时间比食用益生菌和菊粉的大鼠更长。食用合生元的大鼠，但不是食用乳酸杆菌和菊粉的大鼠，其EPM诱发的CORT水平低于对照组。在一个未经处理的队列中评估的基础CORT水平，食用乳酸杆菌和菊粉的大鼠高于对照组。在未经处理的食用合生元的大鼠中，齿状回和海马体1层（CA1）的5-羟色胺mRNA水平高于所有其他未经处理的组，而食用细菌的大鼠海马体5-羟色胺蛋白质水平低于对照组。5-羟色胺mRNA的变化表明肠道微生物对海马体基因表达机制有复杂影响，可能涉及内源性/外源性细菌和益生元的相互作用。重要的是，年龄也可能影响它们的行为结果。总之，这些数据表明，对幼鼠微生物群的干预在应激时会引发早期行为变化，显然是以一种下丘脑-垂体-肾上腺轴独立的方式。
