Experimental autoimmune encephalomyelitis-associated behavioral syndrome as a model of ‘depression due to multiple sclerosis’

Y. Pollak, E. Orion, I. Goshen, H. Ovadia, R. Yirmiya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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.

Original languageAmerican English
Pages (from-to)533-543
Number of pages11
JournalBrain, Behavior, and Immunity
Issue number5
StatePublished - 2002

Bibliographical note

Funding Information:
The authors thank Orli Bar-Shalev, Shira Gur, Lior Friedman, Yael Perets, Meital Shahar, Michal Shlayer, Michal Shuker, and Gilli Wolf for their excellent help in running the experiments. The research was supported by a grant from the Israel Science Foundation (No. 820/00-1), and in part by the Lena P. Harvey Endowment Fund for Neurological Research. RY is a member of the Eric Roland Center for Neurodegenerative Diseases at the Hebrew University of Jerusalem.


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