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Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration

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2015
Authors
Drakulić, Dunja R.
Stanojlović, Miloš R.
Nedeljkovic, Nadezda
Grković, Ivana
Velickovic, Natasa
Guševac, Ivana
Mitrović, Nataša Lj.
Buzadzic, Ivana
Horvat, Anica
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Abstract
Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under t...he influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

Keywords:
Dexamethasone / Ectonucleotidases / Synaptic membranes / Hippocampus
Source:
Journal of Molecular Neuroscience, 2015, 55, 4, 959-967
Projects:
  • Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals (RS-173044)
  • Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (RS-41014)

DOI: 10.1007/s12031-014-0452-y

ISSN: 0895-8696; 1559-1166

PubMed: 25367797

WoS: 000351090800017

Scopus: 2-s2.0-84925463493
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URI
http://vinar.vin.bg.ac.rs/handle/123456789/446
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Vinča

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