Antenatal steroid treatment (ANS) is often given to pregnant women who are at risk of preterm birth, to promote fetal organ maturation. The neurodevelopmental side effects of ANS treatment are not fully understood. We will examine the functional development of central auditory synapses after antenatal dexamethasone treatment of pregnant female mice. ATP signaling mediated by P2X2/3 purine receptors increases the activity of Held synapse, a model for studying glutamate transmission in the auditory part of the brainstem. Repeated ANS treatment is known to alter purine signaling in the rat fetal brain through increased expression of ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase 1/CD39) and ecto-5'-nucleotidase (e5'NT/CD73). These results led to the hypothesis that repeated ANS treatment impairs synapse maturation by increasing the expression and activity of ectonucleotidases that determine the extracellular concentrations of ATP and ADP, and the activation of P2 purine receptors (P2R) in the brain. This would reduce the efficiency of information transmission across the synapse and impair synaptic strengthening, which depends on the activation of postsynaptic P2X2/3 receptors during the maturation of the Held synapse. The hypothesis will be tested after repeated ANS treatment in C57BL/6 mice, the expression of P2X2/3 and P2Y1 receptors, and enzymes that regulate the levels of the respective ligands, i.e. NTPDase1/CD39 and NTPDase2, in the auditory part of the brainstem.

Partner in Germany:

Coordinator for Germany: Ivan Milenković

Coordinator for Serbia: Danijela Laketa, Faculty of Biology, University of Belgrade

Team members from IBISS:
Dr. Irena Lavrnja, Department for Neurobiology IBISS