Pollak Y, Orion E, Goshen I, Ovadia H, Yirmiya R
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Brain Behav Immun. 2002 Oct;16(5):533-43. doi: 10.1016/s0889-1591(02)00010-7.
Many medical conditions, including inflammatory diseases such as multiple sclerosis (MS), are often accompanied by a high prevalence of depressive episodes. Inflammatory mediators, such as cytokines, were implicated in illness-associated depressive conditions, both in humans and in animals. For example, MS-associated depression (MSD) was attributed to pathophysiological processes such as immune dysregulation and cerebral inflammation. We have recently documented a depressive-like behavioral syndrome in mice with experimental autoimmune encephalomyelitis (EAE), an established model of MS. In the present paper, we discuss the similarities between the EAE-associated behavioral syndrome (EBS) and MSD, in terms of phenomenology, putative mechanisms and responsiveness to anti-depressive therapy. In particular, we show that: (1) EAE and depression are associated not only with similar behavioral symptomatology, but also with common physiological alterations, including impaired serotonergic neurotransmission, and activation of neuroendocrine (e.g., adrenocortical) and inflammatory cytokine systems; (2) the EBS precedes any neurological deficit during the initial EAE attack, as well as further exacerbations, and remits during recovery and between relapses. Similarly, in many MS patients depression precedes and accompanies the attacks and wanes during remissions; (3) females show increased susceptibility to EBS. Similarly, depression is much more prevalent in women than in men; (4) chronic treatment with the tricyclic anti-depressant imipramine reduced EAE-induced mortality, body-weight loss and behavioral suppression. Similarly, anti-depressant drugs have been used effectively in treating MSD. These findings suggest that the EBS may serve as an animal model for MSD.
许多疾病，包括诸如多发性硬化症（MS）等炎症性疾病，常常伴有高发性的抑郁发作。炎症介质，如细胞因子，在人类和动物的疾病相关抑郁状态中均有涉及。例如，MS相关抑郁（MSD）被归因于免疫失调和脑部炎症等病理生理过程。我们最近在患有实验性自身免疫性脑脊髓炎（EAE）的小鼠中记录到了一种类似抑郁的行为综合征，EAE是一种公认的MS模型。在本文中，我们从现象学、假定机制以及对抗抑郁治疗的反应性等方面，讨论了EAE相关行为综合征（EBS）与MSD之间的相似性。特别是，我们表明：（1）EAE和抑郁症不仅与相似的行为症状相关，还与常见的生理改变有关，包括血清素能神经传递受损，以及神经内分泌（如肾上腺皮质）和炎症细胞因子系统的激活；（2）在最初的EAE发作以及进一步加重期间，EBS先于任何神经功能缺损出现，并在恢复期间和复发之间缓解。同样，在许多MS患者中，抑郁在发作之前出现并伴随发作，在缓解期减弱；（3）雌性对EBS的易感性增加。同样，抑郁症在女性中比在男性中更为普遍；（4）用三环抗抑郁药丙咪嗪进行长期治疗可降低EAE诱导的死亡率、体重减轻和行为抑制。同样，抗抑郁药物已被有效地用于治疗MSD。这些发现表明，EBS可能作为MSD的动物模型。
