We propose an extensive review of the literature about BDNF/TRKB/P75NTR polymorphisms and their consequences on antidepressant efficacy in depressed patients. Five genome-wide association studies and 30 association studies were included. Twenty seven studies focused on the Val66Met polymorphism (rs6265), the Met allele being associated with a higher antidepressant efficacy only in Asian patients. Other BDNF/TRKB/P75NTR polymorphisms (BDNF: rs7103411, rs7124442, rs908867, rs2049046, rs61888800, rs10501087, rs1491850; TRKB: rs10868223, rs11140778, rs1565445, rs1659412; P75NTR: rs2072446) were reported to be associated with antidepressant efficacy but these results were not replicated. Finally, there are 15 positive studies among 30 studies regarding BDNF/TRKB/P75NTR polymorphisms. The only SNP which benefits of at least three positive studies is the BDNF Val66Met polymorphism (rs6265). Consequently, with a lack of good and consistent studies, the clinical utility of BDNF in treatment selection is far from clear. We propose several recommendations for further studies.
During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg -1 i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.
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