PSA-NCAM is required for antidepressant efficacy

Antidepressant drugs are too often ineffective, the exact mechanism of efficacy is still ambiguous, and there has been a paucity of novel targets for pharmacotherapy. In an attempt to understand the pathogenesis of depression and subsequently develop more efficacious antidepressant drugs, multiple theories have been proposed, including the modulation of neurotransmission, the upregulation of neurogenesis and neurotrophic factors, normalizing hypothalamic-pituitary-adrenal (HPA) reactivity, and the reduction of neuroinflammation; all of which have supporting lines of evidence. Therefore, an ideal molecular target for novel pharmaceutical intervention would function at the confluence of these theories. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) functions broadly, serving to mediate synaptic plasticity, neurogenesis, neurotrophic factor signalling, and inflammatory signalling throughout the brain; all of which are associated with the pathophysiology and treatment of depression. Moreover, the expression of PSA-NCAM is reduced by depression, and conversely enhanced by antidepressant treatment, particularly within the hippocampus. Here we demonstrate that selectively degrading the polysialic acid moiety using the bacteriophage-derived enzyme endoneuraminidase N, completely inhibits the antidepressant efficacy of the selective-serotonin reuptake inhibitor fluoxetine (FLX) in a chronic unpredictable stress model of depression. We also observe a corresponding attenuation of FLX-induced hippocampal neuroplasticity, including decreased hippocampal neurogenesis, synaptic density, and neural activation. These data indicate that PSA-NCAM-mediated neuroplasticity is necessary for antidepressant action; therefore PSA-NCAM represents an interesting, and novel, target for pharmacotherapy.Arts, Faculty ofMedicine, Faculty ofNon UBCPsychology, Department ofReviewedFacultyGraduateUndergraduateOthe

Overweight in young males reduces in a half the normal pregnancy success in rabbit model

[EN] Semen quality has certainly declined over the past few decades, possibly owing to modern lifestyle factors. In this sense, the role of overweight and obesity in the development of subfertility in males has generated a considerable amount of interest in recent years. However, there is no consensus on whether overweight or obesity impaired sperm quality. Thus, based on the ongoing debate about risk factors for subfertility associated with overweight and obesity in men, this study was designed to investigate the effect of overweight on sperm quality parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed to satiety from 12 to 32 weeks of age. At 24 weeks of age, semen samples were analysed weekly by conventional semen analysis for 8 weeks. In addition, during the trial female rabbits were artificially inseminated by each male to assess the fertility success and the number of offspring. Young males fed to satiety were associated with a significant increase in body weight (13.6% overweight) and perirenal fat thickness (5%). Male overweight presented a significant decrease in sperm concentration. There were no differences in the remaining sperm parameters. However, male overweight showed a clear and significant decrease in fertility success (control group, 64±8.9% versus fed to satiety group, 35±9.2%), but not in the number of offspring. Taken together, our findings provide new evidence on the loss of fertility induced by overweight in males.This research was supported by the projects: Spanish Research project AGL2014-5 3405-C2-1-P Comision Interministerial de Ciencia y Tecnologia (FMJ, JSV). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marco-Jiménez, F.; Vicente Antón, JS. (2017). Overweight in young males reduces in a half the normal pregnancy success in rabbit model. PLoS ONE. 12(7):1-11. https://doi.org/10.1371/journal.pone.0180679S11112