NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment
2021
Authors:
Laketa, DanijelaManojlović-Stojanoski, Milica
Lavrnja, Irena
Stevanović, Ivana
Trifunović, Svetlana
Ristić, Nataša
Nestorović, Nataša
Sévigny, Jean
Nedeljković, Nadežda
Contributors
Hess, GrzegorzRukšėnas, Osvaldas
Document Type:
Conference object (Published version)
,
© 2021 by the Federation of European Neuroscience Societies
Metadata
Show full item recordAbstract:
To accelerate organ maturation and prevent complications due to preterm birth, antenatal treatment with
synthetic glucocorticoids (GCs – dexamethasone or betamethasone) is usually given between the 24th
and 34th week of pregnancy to women at risk of delivery within the next seven days [1]. Despite recommendations,
repeat courses of antenatal GCs are frequently given, although excessive GC stimulation may
exert adverse neurodevelopmental effects [1]. The purinergic system is essential for neurodevelopment
[2]. Extracellular purine levels are regulated by ectonucleotidases, with ectonucleoside triphosphate diphosphohydrolase
1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), abundant in the CNS,
which jointly hydrolyze ATP to adenosine. Both ectonucleotidases are also involved in cell adhesion
and migration [3]. We aimed to explore the effects of antenatal dexamethasone (DEX) treatment on the
expression and enzymatic activity of NTPDase1/e5ʹNT tandem in the rat fetal brain. Wistar rat dams were
treated with 0.5 mg/kg DEX, at gestation day (GD) 16, 17, and 18. We found sex-specific male-biased
upregulation of CD39 and CD73 mRNA and protein abundances, and an increase in the corresponding enzymatic activities in the rat fetal brain at GD21, induced by antenatal DEX treatment. Observed changes
indicate a possible decrease in P2, and an increase in P1 purinergic receptors-mediated signaling, as
well as a potential decrease in migration of progenitor cells, particularly pronounced in the brain of male
fetuses. Together, sex-dependent induction of CD39 and CD73 might interfere with neurodevelopmental
processes, thus contributing to adverse effects of antenatal DEX treatment, especially in males.
Keywords:
ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39); ecto-5ʹ-nucleotidase (e5ʹNT/CD73); dexamethasoneFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
- University of Defense (grant number MFVMA/04/19-21
- Natural Sciences and Engineering Research Council of Canada (NSERC; RGPIN-2016-05867)
In:
- Hess G, Rukšėnas O, editors. Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland. Federation of European Neuroscience Societies; 2021. p.