title: 17β-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes.
abstract: 17β-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Mitrović
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Zarić
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia.
authors.forename: Dunja
authors.initials: D
authors.lastname: Drakulić
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinović
authors.affiliation: Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 0A6, Canada.|Centre de recherche du CHU de Québec, Université Laval, Québec, QC, G1V 4G2, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Sévigny
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Stanojlović
authors.affiliation: Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 3, Belgrade, 11000, Serbia.
authors.forename: Nadežda
authors.initials: N
authors.lastname: Nedeljković
authors.affiliation: Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, 11001, Serbia. istanojevic@vinca.rs.
authors.forename: Ivana
authors.initials: I
authors.lastname: Grković
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D055495:Neurogenesis; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D004967:Estrogens; D004958:Estradiol; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001081:Apyrase; C067869:CD39 antigen
keywords: 17β-estradiol; Ectonucleotidase; Hippocampus; Male rats; Synaptic proteins; Synaptosomes