MP81-01 CENTRAL TUMOR NECROSIS FACTOR-ALPHA BLOCKADE INCREASED NNOS EXPRESSION IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND IMPROVED SEXUAL BEHAVIOR DISORDER IN MALE DIABETIC RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology II1 Apr 2017MP81-01 CENTRAL TUMOR NECROSIS FACTOR-ALPHA BLOCKADE INCREASED NNOS EXPRESSION IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND IMPROVED SEXUAL BEHAVIOR DISORDER IN MALE DIABETIC RATS Ting Long, Huanhuan Wang, Xiaohong Ye, Wenwen Lin, Yuanyuan Zhang, and Danian Qin Ting LongTing Long More articles by this author , Huanhuan WangHuanhuan Wang More articles by this author , Xiaohong YeXiaohong Ye More articles by this author , Wenwen LinWenwen Lin More articles by this author , Yuanyuan ZhangYuanyuan Zhang More articles by this author , and Danian QinDanian Qin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2527AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sexual dysfunction, including decreased libido, sexual behavior disorder and erectile dysfunction (ED), is common in male patients with diabetes mellitus (DM). We previously demonstrated that increased peripheral tumor necrosis factor alpha (TNF-a) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-a in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-a inhibition, i.e. etanercept (ETN) via chronic intra-cerebroventricular (ICV) infusion on neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN) and sexual behavior disorder in male diabetic rats. METHODS Type II male DM rats were divided into 4 groups (G), n= 12/G, and subjected to chronic ICV infusion of artificial cerebrospinal fluid (aCSF) or ETN (10 μg/kg/day) by Osmotic Pumps, with and without induction of DM: G1: non-diabetic+ICV aCSF as control; G2: non-diabetic+ICV ETN; G3: DM+ICV aCSF; and G4: DM+ICV ETN. After 4 weeks of treatments, sexual behavior, expression of TNF-a, TNFR-1, and nNOS proteins, nNOS activity, and reactive oxygen species (ROS) generation within the PVN were assessed. RESULTS Male diabetic rats with ICV aCSF treatment displayed significantly severe sexual disorder accompanied with blunted nNOS expression and activity in the PVN in addition to local upregulated TNF-a and TNFR-1 expression, and increased ROS generation compared with non-diabetic controls. The sexual behavioral parameters including mounting latency, intromission latency, the number of mountings and the number of intromissions until ejaculation, induced by the introduction of receptive females, were significantly improved in the treated group with ETN. ICV ETN significantly inhibited TNF-a and TNFR-1 expression and reduced ROS generation in the PVN in diabetic rats. In addition, ICV ETN appeared to induce marked increased in nNOS expression in the PVN of diabetic animals compared with ICV aCSF-treated diabetic rats. Activity of nNOS in the PVN was also significantly increased in ICV ETN-treated versus ICV aCSF-treated diabetic rats. CONCLUSIONS Increased TNF-a and TNFR1 expression in the hypothalamic PVN associated with DM contributes to male sexual disorder by centrally inhibiting nNOS expression and activity in the PVN via promoting local ROS generation. Central TNF-a blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1089 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ting Long More articles by this author Huanhuan Wang More articles by this author Xiaohong Ye More articles by this author Wenwen Lin More articles by this author Yuanyuan Zhang More articles by this author Danian Qin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...