Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail.</p> <p>Results</p> <p>THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells.</p> <p>Conclusion</p> <p>CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.</p

Peritoneal dialysis can be an option for unplanned chronic dialysis: initial results from a developing country

Aim: Starting dialysis in an unplanned manner is frequent situation in dialysis center even for patients with regular nephrology follow-up. Peritoneal dialysis (PD) appears as an option for unplanned initiation of chronic dialysis, offering the advantage of not using central venous catheters and preserving of residual renal function. Since July 2014, we have offered PD as urgent start for chronic kidney disease (CKD) patients. Methods: It was a prospective study that aimed to evaluate the mortality rate in hospitalized patients who started unplanned urgent PD in the first 90 days. It was used high-volume PD right after (<48 h) PD catheter placement, and it was kept until metabolic and fluid controls were achieved. After hospital discharge, patients were treated with intermittent PD on alternate days at the dialysis unit until family training. Results: Thirty-five patients were included from July 2014 to January 2015. Age was 57.7 ± 19.2 years, diabetes was the main etiology of CKD (40.6 %), and uremia was the main dialysis indication (54.3 %). Metabolic and fluid controls were achieved after five sessions of high-volume PD, and patients remained in intermittent PD for 23.2 ± 7.2 days receiving 11.5 ± .3.1 intermittent PD sessions. Peritonitis and mechanical complications occurred in 14.2 and 25.7 %, respectively. Mortality rate was 20 %, and technique survival was 85.7 %. The chronic PD program presented a growth of 41.1 %. Conclusion: The concept of unplanned start on chronic PD may be feasible, safe, complementary alternative to hemodialysis and a tool to increase the PD penetration rate among incident patients starting dialysis therapy.Botucatu School of Medicine, Distrito de Rubião Junio