Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, United States; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH, United States.
Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, United States.
Pharmacol Biochem Behav. 2020 Oct;197:172993. doi: 10.1016/j.pbb.2020.172993. Epub 2020 Jul 11.
Stress exposure can produce profound changes in physiology and behavior that can impair health and well-being. Of note, stress exposure is linked to anxiety disorders and depression in humans. The widespread impact of these disorders warrants investigation into treatments to mitigate the harmful effects of stress. Pharmacological treatments fail to help many with these disorders, so recent work has focused on non-pharmacological alternatives. One of the most promising of these alternatives is environmental enrichment (EE). In rodents, EE includes social, physical, and cognitive stimulation for the animal, in the form of larger cages, running wheels, and toys. EE successfully reduces the maladaptive effects of various stressors, both as treatment and prophylaxis. While we know that EE can have beneficial effects under stress conditions, the morphological and molecular mechanisms underlying these behavioral effects are still not well understood. EE is known to alter neurogenesis, dendrite development, and expression of neurotrophic growth factors, effects that vary by type of enrichment, age, and sex. To add to this complexity, EE has differential effects in different brain regions. Understanding how EE exerts its protective effects on morphological and molecular levels could hold the key to developing more targeted pharmacological treatments. In this review, we summarize the literature on the morphological and molecular consequences of EE and stress in key emotional regulatory pathways in the brain, the hippocampus, prefrontal cortex, and amygdala. The similarities and differences among these regions provide some insight into stress-EE interaction that may be exploited in future efforts toward prevention of, and intervention in, stress-related diseases.
应激暴露会在生理和行为上产生深刻的变化，从而损害健康和幸福感。值得注意的是，应激暴露与人类的焦虑症和抑郁症有关。这些疾病的广泛影响需要研究治疗方法来减轻应激的有害影响。药物治疗未能帮助许多患有这些疾病的人，因此最近的工作集中在非药物替代方法上。其中最有前途的替代方法之一是环境丰富（EE）。在啮齿动物中，EE 包括为动物提供社交、身体和认知刺激，形式为更大的笼子、跑步轮和玩具。EE 成功地减轻了各种应激源的适应不良影响，无论是作为治疗还是预防。虽然我们知道 EE 在应激条件下可以产生有益的影响，但这些行为影响的形态和分子机制仍不清楚。EE 已知会改变神经发生、树突发育和神经营养生长因子的表达，这些影响因丰富类型、年龄和性别而异。为了增加这种复杂性，EE 在不同的大脑区域有不同的影响。了解 EE 如何在形态和分子水平上发挥其保护作用，可能是开发更有针对性的药物治疗方法的关键。在这篇综述中，我们总结了关于 EE 和应激对大脑中关键情绪调节途径（海马体、前额叶皮层和杏仁核）的形态和分子后果的文献。这些区域之间的相似性和差异为应激-EE 相互作用提供了一些见解，这可能有助于未来预防和干预与应激相关的疾病。
