engleski

Serotonin uptake into human cord blood platelets: modulation by maternal metabolic state

Serotonin (5HT) plays a crucial role in fetal brain development by regulating the outgrowth of its own neurons and the maturation of their target regions. In adults, active levels of 5HT in the blood are tightly controlled by the highaffinity uptake of 5HT into platelets. The aim of the present study was to examine the presence of an analogous 5HT uptake system in the fetal circulation and investigate its potential modulation by maternal gestational diabetes mellitus (GDM). The study was performed on mothernewborn pairs recruited at the Clinical Hospital Centre Zagreb, Croatia, as a part of our ongoing birth cohort study PlaNS (Placental and Neonatal Serotonin). Cord blood samples were collected via umbilical venipuncture immediately after baby birth. Platelet rich plasma (PRP) was isolated by centrifugation and 5HT uptake kinetics was studied using a radiotracerbased assay. Mean platelet volumes in whole cord blood and PRP samples were highly correlated, demonstrating that population of platelets isolated in PRP represented well platelets in the whole cord blood samples. Neonatal platelets showed efficient, timeand temperaturedependent 5HT uptake, with initial rates of specific 5HT transport saturable over the highaffinity range of 5HT concentrations (0.1 to 2.0 μM). In all subjects tested, values of Michaelis affinity constant (Km) and maximal transport velocity (Vmax) were characteristic of the uptake1 (highaffinity / lowcapacity) transport mechanism, and comparable to those in adult platelets. Further, 5HT transport into cord blood platelets was compromised by maternal GDM, due to decreased substrate affinity (increased Km value). In conclusion, data provide the first demonstration of a functional system for 5HT uptake in human neonatal platelets and suggest that it could represent a potential mechanism mediating the influence of GDM on fetal brain development.

serotonin uptake system ; platelet rich plasma ; cord blood ; gestational diabetes mellitus (GDM)

nije evidentirano