Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1β

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• 作者：Andrey M. Mazarati ; Eduardo Pineda ; Don Shin ; Delia Tio ; Anna N. Taylor ; Raman Sankar
• 关键词：Temporal lobe epilepsy ; Depression ; Comorbidity ; Brain inflammation ; Interleukin-1β ; Hippocampus
• 刊名：Neurobiology of Disease
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：37
• 期：2
• 页码：461-467
• 全文大小：579 K

文摘

Depression is a frequent comorbidity of temporal lobe epilepsy (TLE); however, its mechanisms remain poorly understood and effective therapies are lacking. Augmentation of hippocampal interleukin-1β (IL-1β) signaling may be a mechanistic factor of both TLE and clinical depression. We examined whether pharmacological blockade of hippocampal interleukin-1 receptor exerts antidepressant effects in an animal model of comorbidity between TLE and depression, which developed in Wistar rats following pilocarpine status epilepticus (SE). In post-SE animals, depression-like state was characterized by behavioral equivalents of anhedonia and despair; dysregulation of the hypothalamo–pituitary–adrenocortical axis; compromised raphe–hippocampal serotonergic transmission. Two-week long bilateral intrahippocampal infusion of human recombinant Interleukin-1 receptor antagonist (IL-1ra) improved all of the examined depressive impairments, without modifying spontaneous seizure frequency and without affecting normal parameters in naïve rats. These findings implicate hippocampal IL-1β in epilepsy-associated depression and provide a rationale for the introduction of IL-1β blockers in the treatment of depression in TLE.