Comorbidity between epilepsy and depression: role of hippocampal interleukin-1beta

• Published in: Neurobiology of disease 2010-02, Vol.37 (2), p.461
• Main Authors: Mazarati, Andrey M, Pineda, Eduardo, Shin, Don, Tio, Delia, Taylor, Anna N, Sankar, Raman
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Comorbidity; Convulsants - pharmacology; Depressive Disorder - drug therapy; Depressive Disorder - immunology; Depressive Disorder - physiopathology; Disease Models, Animal; Epilepsy - complications; Epilepsy - immunology; Epilepsy - physiopathology; Hippocampus - immunology; Hippocampus - metabolism; Hippocampus - physiopathology; Hypothalamo-Hypophyseal System - physiopathology; Interleukin 1 Receptor Antagonist Protein - pharmacology; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - metabolism; Male; Neural Pathways - physiopathology; Pilocarpine - pharmacology; Pituitary-Adrenal System - physiopathology; Raphe Nuclei - physiopathology; Rats; Rats, Wistar; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - metabolism; Status Epilepticus - chemically induced; Status Epilepticus - complications; Status Epilepticus - physiopathology
• ISSN: 1095-953X
• DOI: 10.1016/j.nbd.2009.11.001

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-1beta (IL-1beta) 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-1beta in epilepsy-associated depression and provide a rationale for the introduction of IL-1beta blockers in the treatment of depression in TLE.