Login to Access Video or Poster Abstract: MP81-01
Sources of Funding: Guangdong Province Characteristic Innovation Project (China, 2015KTSCX044) (PI, Ting Long).

Introduction

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-?) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-? in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-? 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 ?g/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-?, 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-? 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-? 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-? 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-? blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN.

Funding

Guangdong Province Characteristic Innovation Project (China, 2015KTSCX044) (PI, Ting Long).