Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
PLoS One. 2013;8(1):e54811. doi: 10.1371/journal.pone.0054811. Epub 2013 Jan 17.
Environmental enrichment (EE) has a beneficial effect on rodent behaviour, neuronal plasticity and brain function. Although it may also improve stress coping, it is not known whether EE influences the brain response to an external (psychological) stressor such as water avoidance stress (WAS) or an internal (systemic) stressor such as gastrointestinal inflammation. This study hence explored whether EE modifies WAS-induced activation of the mouse corticolimbic system and whether this stress response is altered by gastritis or colitis. Male C67BL/6N mice were housed under standard or enriched environment for 9 weeks, after which they were subjected to a 1-week treatment with oral iodoacetamide to induce gastritis or oral dextran sulfate sodium to induce colitis. Following exposure to WAS the expression of c-Fos, a marker of neuronal activation, was measured by immunocytochemistry. EE aggravated experimentally induced colitis, but not gastritis, as shown by an increase in the disease activity score and the colonic myeloperoxidase content. In the brain, EE enhanced the WAS-induced activation of the dentate gyrus and unmasked an inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression within this part of the hippocampus. Conversely, EE inhibited the WAS-evoked activation of the central amygdala and prevented the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this region. EE, in addition, blunted the WAS-induced activation of the infralimbic cortex and attenuated the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this area. These data reveal that EE has a region-specific effect on stress-induced c-Fos expression in the corticolimbic system, which is likely to improve stress resilience. The response of the prefrontal cortex - amygdala - hippocampus circuitry to psychological stress is also modified by the systemic stress of gut inflammation, and this interaction between external and internal stressors is modulated by the housing environment.
环境富集（EE）对啮齿动物的行为、神经元可塑性和大脑功能有有益的影响。尽管它也可能改善压力应对能力，但尚不清楚 EE 是否会影响大脑对外界（心理）应激源（如回避水应激（WAS））或内部（系统性）应激源（如胃肠道炎症）的反应。因此，本研究探讨了 EE 是否会改变 WAS 诱导的小鼠皮质边缘系统的激活，以及这种应激反应是否会因胃炎或结肠炎而改变。雄性 C67BL/6N 小鼠在标准或丰富环境中饲养 9 周后，接受为期 1 周的口服碘乙酰胺诱导胃炎或口服葡聚糖硫酸钠诱导结肠炎治疗。暴露于 WAS 后，通过免疫细胞化学测量神经元激活标志物 c-Fos 的表达。EE 加重了实验性诱导的结肠炎，但没有加重胃炎，这表现为疾病活动评分和结肠髓过氧化物酶含量的增加。在大脑中，EE 增强了 WAS 诱导的齿状回激活，并揭示了胃炎和结肠炎对海马这一部分中 WAS 诱发的 c-Fos 表达的抑制作用。相反，EE 抑制了 WAS 诱导的中杏仁核的激活，并防止了胃炎和结肠炎对 WAS 诱导的 c-Fos 表达在该区域的抑制作用。此外，EE 减弱了 WAS 诱导的下边缘皮质的激活，并减轻了胃炎和结肠炎对 WAS 诱导的 c-Fos 表达在该区域的抑制作用。这些数据表明，EE 对皮质边缘系统中应激诱导的 c-Fos 表达具有特定的区域效应，这可能会提高应激耐受力。前额叶皮层-杏仁核-海马回路对心理应激的反应也受到肠道炎症系统性应激的影响，而这种外部和内部应激源之间的相互作用受到居住环境的调节。
