NISE Laboratory, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, Ontario K1N 6N5, Canada.
NISE Laboratory, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, Ontario K1N 6N5, Canada; University of Ottawa Brain and Mind Research Institute, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, Ontario K1N 6N5, Canada.
Brain Res Bull. 2021 Dec;177:111-118. doi: 10.1016/j.brainresbull.2021.09.017. Epub 2021 Sep 22.
Puberty is a period of rapid cortical and neuronal development. Stress exposure during puberty programs the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to future stressors. However, programming can result in an enduring maladaptation of the HPA axis activity and can be associated with long-term anxiety- and depression-like behaviours. Probiotic treatment mitigates the effect of stress on mental health, suggesting that the gut microbiome may mediate the programming of the HPA axis. However, the mechanism underlying this effect remains elusive. Thus, we investigated the effect of probiotic exposure on lipopolysaccharide (LPS)-induced programming of the HPA axis and glucocorticoid receptor (GR) expression in the paraventricular (PVN), basolateral amygdala (BLA), piriform cortex (PIR), and medial prefrontal cortex (mPFC). Male and female mice were exposed to either probiotics or control skim milk and were treated with either saline or LPS during puberty. Prior to euthanasia in adulthood, mice were restrained for 30 min. The results showed that pubertal LPS treatment permanently decreased GR expression in the PVN in milk fed control males. However, pubertal probiotic treatment blocked the LPS-induced decrease in GR expression in males. Given that this effect is limited to males, further research is required to better understand sex differences in the interactions between the gut microbiome and the programming of the HPA axis during puberty. Nevertheless, our findings suggest that the gut microbiome influences the neurophysiology of the HPA axis and mediates its programming in pubertal males. The prevention of GR reduction in the male PVN and PIR using probiotics illustrates the complexity of the gut-brain communication and compels continued investigation.
青春期是大脑皮层和神经元快速发育的时期。青春期暴露于应激会导致下丘脑-垂体-肾上腺（HPA）轴对未来应激源的反应性编程。然而，这种编程可能导致 HPA 轴活动的持久适应不良，并与长期的焦虑和抑郁样行为相关。益生菌治疗减轻了应激对心理健康的影响，这表明肠道微生物组可能介导了 HPA 轴的编程。然而，这种效应的机制仍然难以捉摸。因此，我们研究了益生菌暴露对脂多糖（LPS）诱导的 HPA 轴编程和室旁核（PVN）、外侧杏仁核（BLA）、梨状皮层（PIR）和内侧前额叶皮层（mPFC）中糖皮质激素受体（GR）表达的影响。雄性和雌性小鼠分别暴露于益生菌或对照脱脂奶中，并在青春期接受盐水或 LPS 治疗。在成年期安乐死之前，将小鼠束缚 30 分钟。结果表明，青春期 LPS 处理会永久性地降低雄性牛奶喂养对照组 PVN 中的 GR 表达。然而，青春期益生菌处理阻止了 LPS 诱导的雄性 GR 表达下降。由于这种效应仅限于雄性，因此需要进一步研究以更好地理解肠道微生物组和青春期 HPA 轴编程之间相互作用的性别差异。尽管如此，我们的研究结果表明，肠道微生物组影响 HPA 轴的神经生理学，并介导其在青春期雄性中的编程。使用益生菌预防雄性 PVN 和 PIR 中 GR 的减少说明了肠道-大脑通讯的复杂性，并促使继续进行研究。
