Depression induced by chronic stress leads to penile cavernosal dysfunction: protective effect of anti-TNF-α treatment

• Published in: Canadian journal of physiology and pharmacology Vol. 96; no. 9; pp. 933 - 942
• Main Authors: Demirtaş Şahin, Tuğçe, Yazir, Yusufhan, Utkan, Tijen, Gacar, Gulcin, Halbutoğulları, Zehra Seda, Gocmez, Semil Selcen
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.09.2018; Canadian Science Publishing NRC Research Press
• Subjects: Animal models; Animals; Cell adhesion; Corticosterone; Cytokines; dysfonction érectile; Endothelium; Erectile dysfunction; Etanercept; Exposure; IL-1β; Inflammation; Intercellular adhesion molecule 1; Interleukin 6; Mental depression; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Nitric oxide; Nitric-oxide synthase; Penis; Pharmacology; Physiology; Rats; stress léger imprévisible chronique; Testosterone; TNF-α; Tumor necrosis factor-TNF; Tumor necrosis factor-α; unpredictable chronic mild stress; unpredictable chronic mild stress; dysfonction érectile; stress léger imprévisible chronique; TNF-α; inflammation; erectile dysfunction
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0778

Psychological stress may lead to erectile dysfunction (ED), and inflammation has been evaluated as a major contributing factor. The goal of this study was to investigate the effects of etanercept (ETN), an anti-tumor necrosis factor α (TNF-α) protein, on cavernosal function in the unpredictable chronic mild stress (UCMS) rat model of depression. Animals were divided into 4 groups: animals not exposed to UCMS, animals not exposed to UCMS and treated with ETN, animals exposed to UCMS, and animals treated with ETN while exposed to UCMS. UCMS significantly impaired the neurogenic and endothelium-dependent relaxation responses; reduced cavernosal endothelial nitric oxide (NO) synthase (eNOS) and neuronal NO synthase (nNOS) expressions; decreased testosterone levels; enhanced systemic levels of corticosterone, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule 1 (ICAM-1); and also increased cavernosal levels of TNF-α, IL-1β, and IL-6 in rats. ETN administration restored NO-mediated neurogenic and endothelium-dependent relaxation responses of the corpus cavernosum, increased cavernosal eNOS and nNOS expressions, enhanced testosterone levels, and decreased corticosterone levels in UCMS-exposed rats. Also, systemic inflammatory markers and cavernosal proinflammatory cytokine levels were reduced by ETN. Our results demonstrate the role of TNF-α-mediated inflammation in the development of depression and ED in rats exposed to chronic stress.