Filipović Dragana, Todorović Nevena, Bernardi Rick E, Gass Peter
Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinča", University of Belgrade, PO Box 522-090, 11001, Belgrade, Serbia.
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany.
Brain Struct Funct. 2017 Jan;222(1):1-20. doi: 10.1007/s00429-016-1218-9. Epub 2016 Mar 31.
Various stressors may disrupt the redox homeostasis of an organism by causing oxidative and nitrosative stress that may activate stressor-specific pathways and provoke specific responses. Chronic social isolation (CSIS) represents a mild chronic stress that evokes a variety of neurobehavioral changes in rats similar to those observed in people with psychiatric disorders, including depression. Most rodent studies have focused on the effect of social isolation during weaning or adolescence, while its effect in adult rats has not been extensively examined. In this review, we discuss the current knowledge regarding the involvement of oxidative/nitrosative stress pathways in the prefrontal cortex and hippocampus of adult male rats exposed to CSIS, focusing on hypothalamic-pituitary-adrenocortical (HPA) axis activity, behavior parameters, antioxidative defense systems, stress signaling mediated by nuclear factor-kappa B (NF-κB), and mitochondria-related proapoptotic signaling. Although increased concentrations of corticosterone (CORT) have been shown to induce oxidative and nitrosative stress, we suggest a mechanism underlying the glucocorticoid paradox whereby a state of oxidative/nitrosative stress may exist under basal CORT levels. This review also highlights the differential susceptibility of prefrontal cortex and hippocampus to oxidative stress following CSIS and suggests a possible cellular pathway of stress tolerance that preserves the hippocampus from molecular damage and apoptosis. The differential regulation of the transcriptional factor NF-κB, and the enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) following CSIS may be one functional difference between the response of the prefrontal cortex and hippocampus, thus identifying potentially relevant targets for antidepressant treatment.
各种应激源可能通过引起氧化应激和亚硝化应激来破坏生物体的氧化还原稳态，这可能会激活应激源特异性途径并引发特定反应。慢性社会隔离（CSIS）是一种轻度慢性应激，会在大鼠中引发各种神经行为变化，类似于在患有精神疾病（包括抑郁症）的人群中观察到的变化。大多数啮齿动物研究都集中在断奶期或青春期社会隔离的影响上，而其对成年大鼠的影响尚未得到广泛研究。在这篇综述中，我们讨论了关于氧化/亚硝化应激途径在成年雄性大鼠暴露于CSIS后的前额叶皮质和海马体中的作用的现有知识，重点关注下丘脑-垂体-肾上腺皮质（HPA）轴活性、行为参数、抗氧化防御系统、由核因子-κB（NF-κB）介导的应激信号以及与线粒体相关的促凋亡信号。尽管已证明皮质酮（CORT）浓度升高会诱导氧化应激和亚硝化应激，但我们提出了一种糖皮质激素悖论的潜在机制，即在基础CORT水平下可能存在氧化/亚硝化应激状态。这篇综述还强调了CSIS后前额叶皮质和海马体对氧化应激的不同易感性，并提出了一种可能的应激耐受细胞途径，该途径可保护海马体免受分子损伤和凋亡。CSIS后转录因子NF-κB以及诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的差异调节可能是前额叶皮质和海马体反应之间的一个功能差异，从而确定了抗抑郁治疗的潜在相关靶点。
