Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors

Depression is a chronic and recurrent disorder, associated with high morbidity and risk of suicide. Leptin was firstly described as an anti-obesity hormone, but several actions of leptin in CNS have been reported. In fact, leptin regulates dopaminergic neurotransmission in mesolimbic areas and has antidepressant-like properties in stress-based models. In the present study, we investigated, for the first time, putative antidepressant-like effects of leptin in an animal model of depressive-like behaviors induced by lipopolysaccharide (LPS), and the potential involvement of dopamine receptors as mediators of those behavioral effects. Mice were injected leptin (1.5 mg/kg, IP) or imipramine prior to LPS administration. To evaluate the involvement of dopamine receptors, different experimental groups were pretreated with either the dopaminergic antagonist SCH23390, for D1 receptors or raclopride, for D2/D3 receptors, prior to leptin injection. Twenty-four hours post-LPS, mice were submitted to the forced swimming and sucrose preference tests. In addition, IL-1β levels were determined in the prefrontal cortex (PFC), hippocampus and striatum. BDNF levels were measured in the hippocampus. Our results showed that leptin, similarly to imipramine, prevented the core behavioral alterations induced by LPS (despair-like behavior and anhedonia), without altering locomotion. In neurochemical analysis, leptin restored LPS-induced changes in IL-1β levels in the PFC and striatum, and increased BDNF levels in the hippocampus. The blockade of dopamine D1 and D2/D3 receptors inhibited leptin's antidepressant-like effects, whilst only the blockade of D1-like receptors blunted leptin-induced increments in prefrontal IL-1β levels. Our results indicate that leptin has antidepressant-like effects in an inflammatory model of depression with the contribution, at least partial, of dopamine receptors

Mitral regurgitation after percutaneous mitral valvuloplasty : insights into mechanisms and impact on clinical outcomes

Objectives: The aim of this study was to assess the incidence, mechanisms, and outcomes of mitral regurgitation (MR) after percutaneous mitral valvuloplasty (PMV). Background: Significant MR continues to be a major complication of PMV, with a wide range in clinical presentation and prognosis. Methods: Consecutive patients with mitral stenosis undergoing PMV were prospectively enrolled. MR severity was evaluated by using quantitative echocardiographic criteria, and its mechanism was characterized by 3-dimensional transesophageal echocardiography, divided broadly into 4 categories based on the features contributing to the valve damage. B-type natriuretic peptide levels were obtained before and 24 h after the procedure. Endpoints estimated cardiovascular death or mitral valve (MV) replacement due to predominant MR. Results: A total of 344 patients, ages 45.1 ± 12.1 years, of whom 293 (85%) were women, were enrolled. Significant MR after PMV was found in 64 patients (18.6%). The most frequent mechanism of MR was commissural, which occurred in 22 (34.4%) patients, followed by commissural with posterior leaflet in 16 (25.0%), leaflets at central scallop or subvalvular damage in 15 (23.4%), and central MR in 11 (17.2%). During the mean follow-up period of 3 years (range 1 day to 10.6 years), 60 patients reached the endpoint. The event-free survival rates were similar among patients with mild or commissural MR, whereas patients with damaged central leaflet scallop or subvalvular apparatus had the worst outcome, with an event-free survival rate at 1 year of only 7%. Long-term outcome was predicted by net atrioventricular compliance (Cn) at baseline and post-procedural variables, including valve area, mean gradient, and magnitude of decrease in B-type natriuretic peptide levels, adjusted for the mechanism of MR. Conclusions: Significant MR following PMV is a frequent event, mainly related to commissural splitting, with favorable clinical outcome. Parameters that express the relief of valve obstruction and the mechanism by which MR develops were predictors of long-term outcomes