Skip to main content

Advertisement

Log in

Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression of ecto-enzymes NTPDase1, NTPDase2, and ecto-5′-nucleotidase (eN) after removal of ovaries (OVX) and estradiol replacement (E2) in female rat hippocampus. The results show that target ectonucleotidases are predominantly localized in synapse-rich hippocampal layers. The most represented NTPDase in the hippocampal tissue is NTPDase2, being at the same time the mostly affected ectonucleotidase by OVX and E2. Specifically, OVX decreases the expression of NTPDase2 and eN, whereas E2 restores their expression to control level. Impact of OVX and E2 on ectonucleotidase expression was also examined in purified synaptosome (SYN) and gliosome (GLIO) fractions. Data reveal that SYN expresses NTPDase1 and NTPDase2, both of which are reduced following OVX and restored with E2. GLIO exhibits NTPDase2-mediated ATP hydrolysis, which falls in OVX, and recovers by E2. These changes in the activity occur without parallel changes in NTPDase2-protein abundance. The same holds for eN. The lack of correlation between NTPDase2 and eN activities and their respective protein abundances suggest a non-genomic mode of E2 action, which is studied further in primary astrocyte culture. Since ovarian steroids shape hippocampal synaptic networks and regulate ectonucleotidase activities, it is possible that cognitive deficits seen after ovary removal may arise from the loss of E2 modulatory actions on ectonucleotidase expression in the hippocampus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Prange-Kiel J, Rune GM (2006) Direct and indirect effects of estrogen on rat hippocampus. Neuroscience 138(3):765–772. https://doi.org/10.1016/j.neuroscience.2005.05.061

    Article  CAS  PubMed  Google Scholar 

  2. Lisofsky N, Martensson J, Eckert A, Lindenberger U, Gallinat J, Kuhn S (2015) Hippocampal volume and functional connectivity changes during the female menstrual cycle. NeuroImage 118:154–162. https://doi.org/10.1016/j.neuroimage.2015.06.012

    Article  PubMed  Google Scholar 

  3. Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336(2):293–306. https://doi.org/10.1002/cne.903360210

    Article  CAS  PubMed  Google Scholar 

  4. Brinton RD (2009) Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Pharmacol Sci 30(4):212–222. https://doi.org/10.1016/j.tips.2008.12.006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Galea LA, Uban KA, Epp JR, Brummelte S, Barha CK, Wilson WL, Lieblich SE, Pawluski JL (2008) Endocrine regulation of cognition and neuroplasticity: our pursuit to unveil the complex interaction between hormones, the brain, and behaviour. Can J Exp Psychol 62(4):247–260. https://doi.org/10.1037/a0014501

    Article  PubMed  Google Scholar 

  6. Fester L, Prange-Kiel J, Zhou L, Blittersdorf BV, Bohm J, Jarry H, Schumacher M, Rune GM (2012) Estrogen-regulated synaptogenesis in the hippocampus: sexual dimorphism in vivo but not in vitro. J Steroid Biochem Mol Biol 131(1–2):24–29. https://doi.org/10.1016/j.jsbmb.2011.11.010

    Article  CAS  PubMed  Google Scholar 

  7. Frankfurt M, Luine V (2015) The evolving role of dendritic spines and memory: interaction(s) with estradiol. Horm Behav 74:28–36. https://doi.org/10.1016/j.yhbeh.2015.05.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Frick KM, Kim J, Tuscher JJ, Fortress AM (2015) Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents. Learn Mem 22(9):472–493. https://doi.org/10.1101/lm.037267.114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Hara Y, Waters EM, McEwen BS, Morrison JH (2015) Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol Rev 95(3):785–807. https://doi.org/10.1152/physrev.00036.2014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Sellers K, Raval P, Srivastava DP (2015) Molecular signature of rapid estrogen regulation of synaptic connectivity and cognition. Front Neuroendocrinol 36:72–89. https://doi.org/10.1016/j.yfrne.2014.08.001

    Article  CAS  PubMed  Google Scholar 

  11. Phan A, Suschkov S, Molinaro L, Reynolds K, Lymer JM, Bailey CD, Kow LM, MacLusky NJ et al (2015) Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements. Proc Natl Acad Sci U S A 112(52):16018–16023. https://doi.org/10.1073/pnas.1522150112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Henderson VW (2008) Cognitive changes after menopause: influence of estrogen. Clin Obstet Gynecol 51(3):618–626. https://doi.org/10.1097/GRF.0b013e318180ba10

    Article  PubMed Central  PubMed  Google Scholar 

  13. Krug R, Born J, Rasch B (2006) A 3-day estrogen treatment improves prefrontal cortex-dependent cognitive function in postmenopausal women. Psychoneuroendocrinology 31(8):965–975. https://doi.org/10.1016/j.psyneuen.2006.05.007

    Article  CAS  PubMed  Google Scholar 

  14. Habib P, Beyer C (2015) Regulation of brain microglia by female gonadal steroids. J Steroid Biochem Mol Biol 146:3–14. https://doi.org/10.1016/j.jsbmb.2014.02.018

    Article  CAS  PubMed  Google Scholar 

  15. Sarvari M, Kallo I, Hrabovszky E, Solymosi N, Liposits Z (2014) Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats. PLoS One 9(2):e88540. https://doi.org/10.1371/journal.pone.0088540

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Acaz-Fonseca E, Avila-Rodriguez M, Garcia-Segura LM, Barreto GE (2016) Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions. Prog Neurobiol 144:5–26. https://doi.org/10.1016/j.pneurobio.2016.06.002

    Article  CAS  PubMed  Google Scholar 

  17. Hamilton RT, Rettberg JR, Mao Z, To J, Zhao L, Appt SE, Register TC, Kaplan JR et al (2011) Hippocampal responsiveness to 17beta-estradiol and equol after long-term ovariectomy: implication for a therapeutic window of opportunity. Brain Res 1379:11–22. https://doi.org/10.1016/j.brainres.2011.01.029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gillies GE, McArthur S (2010) Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev 62(2):155–198. https://doi.org/10.1124/pr.109.002071

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Potier M, Georges F, Brayda-Bruno L, Ladepeche L, Lamothe V, Al Abed AS, Groc L, Marighetto A (2016) Temporal memory and its enhancement by estradiol requires surface dynamics of hippocampal CA1 N-methyl-D-aspartate receptors. Biol Psychiatry 79(9):735–745. https://doi.org/10.1016/j.biopsych.2015.07.017

    Article  CAS  PubMed  Google Scholar 

  20. Stanojlovic M, Gusevac I, Grkovic I, Mitrovic N, Zlatkovic J, Horvat A, Drakulic D (2016) Repeated estradiol treatment attenuates chronic cerebral hypoperfusion-induced neurodegeneration in rat hippocampus. Cell Mol Neurobiol 36(6):989–999. https://doi.org/10.1007/s10571-015-0289-0

    Article  CAS  PubMed  Google Scholar 

  21. Sherwin BB (2012) Estrogen and cognitive functioning in women: lessons we have learned. Behav Neurosci 126(1):123–127. https://doi.org/10.1037/a0025539

    Article  CAS  PubMed  Google Scholar 

  22. Schipper HM (2016) The impact of gonadal hormones on the expression of human neurological disorders. Neuroendocrinology 103(5):417–431. https://doi.org/10.1159/000440620

    Article  CAS  PubMed  Google Scholar 

  23. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87(2):659–797. https://doi.org/10.1152/physrev.00043.2006

    Article  CAS  PubMed  Google Scholar 

  24. Burnstock G (2016) An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration. Neuropharmacology 104:4–17. https://doi.org/10.1016/j.neuropharm.2015.05.031

    Article  CAS  PubMed  Google Scholar 

  25. Koles L, Kato E, Hanuska A, Zadori ZS, Al-Khrasani M, Zelles T, Rubini P, Illes P (2016) Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems. Purinergic Signal 12(1):1–24. https://doi.org/10.1007/s11302-015-9480-5

    Article  CAS  PubMed  Google Scholar 

  26. Sebastiao AM, Ribeiro JA (2015) Neuromodulation and metamodulation by adenosine: impact and subtleties upon synaptic plasticity regulation. Brain Res 1621:102–113. https://doi.org/10.1016/j.brainres.2014.11.008

    Article  CAS  PubMed  Google Scholar 

  27. Zimmermann H, Zebisch M, Strater N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8(3):437–502. https://doi.org/10.1007/s11302-012-9309-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Robson SC, Sevigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2(2):409–430. https://doi.org/10.1007/s11302-006-9003-5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Langer D, Hammer K, Koszalka P, Schrader J, Robson S, Zimmermann H (2008) Distribution of ectonucleotidases in the rodent brain revisited. Cell Tissue Res 334(2):199–217. https://doi.org/10.1007/s00441-008-0681-x

    Article  CAS  PubMed  Google Scholar 

  30. Grkovic I, Drakulic D, Martinovic J, Mitrovic N (2017) Role of ectonucleotidases in the synapse formation during brain development: physiological and pathological implications. Curr Neuropharmacol 15. https://doi.org/10.2174/1570159X15666170518151541

  31. Bjelobaba I, Stojiljkovic M, Pekovic S, Dacic S, Lavrnja I, Stojkov D, Rakic L, Nedeljkovic N (2007) Immunohistological determination of ecto-nucleoside triphosphate diphosphohydrolase1 (NTPDase1) and 5′-nucleotidase in rat hippocampus reveals overlapping distribution. Cell Mol Neurobiol 27(6):731–743. https://doi.org/10.1007/s10571-007-9159-8

    Article  CAS  PubMed  Google Scholar 

  32. Wang TF, Guidotti G (1998) Widespread expression of ecto-apyrase (CD39) in the central nervous system. Brain Res 790(1–2):318–322

    Article  CAS  PubMed  Google Scholar 

  33. Braun N, Sevigny J, Robson SC, Enjyoji K, Guckelberger O, Hammer K, Di Virgilio F, Zimmermann H (2000) Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain. Eur J Neurosci 12(12):4357–4366

    CAS  PubMed  Google Scholar 

  34. Brisevac D, Adzic M, Laketa D, Parabucki A, Milosevic M, Lavrnja I, Bjelobaba I, Sevigny J et al (2015) Extracellular ATP selectively upregulates ecto-nucleoside triphosphate diphosphohydrolase 2 and ecto-5'-nucleotidase by rat cortical astrocytes in vitro. J Mol Neurosci 57(3):452–462. https://doi.org/10.1007/s12031-015-0601-y

    Article  CAS  PubMed  Google Scholar 

  35. Jakovljevic M, Lavrnja I, Bozic I, Savic D, Bjelobaba I, Pekovic S, Sevigny J, Nedeljkovic N et al (2017) Down-regulation of NTPDase2 and ADP-sensitive P2 purinoceptors correlate with severity of symptoms during experimental autoimmune encephalomyelitis. Front Cell Neurosci 11:333. https://doi.org/10.3389/fncel.2017.00333

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Wink MR, Braganhol E, Tamajusuku AS, Lenz G, Zerbini LF, Libermann TA, Sevigny J, Battastini AM et al (2006) Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes. Neuroscience 138(2):421–432. https://doi.org/10.1016/j.neuroscience.2005.11.039

    Article  CAS  PubMed  Google Scholar 

  37. Braun N, Sevigny J, Mishra SK, Robson SC, Barth SW, Gerstberger R, Hammer K, Zimmermann H (2003) Expression of the ecto-ATPase NTPDase2 in the germinal zones of the developing and adult rat brain. Eur J Neurosci 17(7):1355–1364

    Article  PubMed  Google Scholar 

  38. Shukla V, Zimmermann H, Wang L, Kettenmann H, Raab S, Hammer K, Sevigny J, Robson SC et al (2005) Functional expression of the ecto-ATPase NTPDase2 and of nucleotide receptors by neuronal progenitor cells in the adult murine hippocampus. J Neurosci Res 80(5):600–610. https://doi.org/10.1002/jnr.20508

    Article  CAS  PubMed  Google Scholar 

  39. Belcher SM, Zsarnovszky A, Crawford PA, Hemani H, Spurling L, Kirley TL (2006) Immunolocalization of ecto-nucleoside triphosphate diphosphohydrolase 3 in rat brain: implications for modulation of multiple homeostatic systems including feeding and sleep-wake behaviors. Neuroscience 137(4):1331–1346. https://doi.org/10.1016/j.neuroscience.2005.08.086

    Article  CAS  PubMed  Google Scholar 

  40. Grkovic I, Bjelobaba I, Mitrovic N, Lavrnja I, Drakulic D, Martinovic J, Stanojlovic M, Horvat A et al (2016) Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development. J Chem Neuroanat 77:10–18. https://doi.org/10.1016/j.jchemneu.2016.04.001

    Article  CAS  PubMed  Google Scholar 

  41. Lavrnja I, Laketa D, Savic D, Bozic I, Bjelobaba I, Pekovic S, Nedeljkovic N (2015) Expression of a second ecto-5′-nucleotidase variant besides the usual protein in symptomatic phase of experimental autoimmune encephalomyelitis. J Mol Neurosci 55(4):898–911. https://doi.org/10.1007/s12031-014-0445-x

    Article  CAS  PubMed  Google Scholar 

  42. Cunha RA (2001) Regulation of the ecto-nucleotidase pathway in rat hippocampal nerve terminals. Neurochem Res 26(8–9):979–991

    Article  CAS  PubMed  Google Scholar 

  43. Kukulski F, Komoszynski M (2003) Purification and characterization of NTPDase1 (ecto-apyrase) and NTPDase2 (ecto-ATPase) from porcine brain cortex synaptosomes. Eur J Biochem 270(16):3447–3454

    Article  CAS  PubMed  Google Scholar 

  44. Stanojevic I, Bjelobaba I, Nedeljkovic N, Drakulic D, Petrovic S, Stojiljkovic M, Horvat A (2011) Ontogenetic profile of ecto-5′-nucleotidase in rat brain synaptic plasma membranes. Int J Dev Neurosci 29(4):397–403. https://doi.org/10.1016/j.ijdevneu.2011.03.003

    Article  CAS  PubMed  Google Scholar 

  45. Grkovic I, Bjelobaba I, Nedeljkovic N, Mitrovic N, Drakulic D, Stanojlovic M, Horvat A (2014) Developmental increase in ecto-5′-nucleotidase activity overlaps with appearance of two immunologically distinct enzyme isoforms in rat hippocampal synaptic plasma membranes. J Mol Neurosci 54(1):109–118. https://doi.org/10.1007/s12031-014-0256-0

    Article  CAS  PubMed  Google Scholar 

  46. Mitrovic N, Zaric M, Drakulic D, Martinovic J, Sevigny J, Stanojlovic M, Nedeljkovic N, Grkovic I (2017) 17beta-estradiol-induced synaptic rearrangements are accompanied by altered ectonucleotidase activities in male rat hippocampal synaptosomes. J Mol Neurosci 61(3):412–422. https://doi.org/10.1007/s12031-016-0877-6

    Article  CAS  PubMed  Google Scholar 

  47. Mitrovic N, Zaric M, Drakulic D, Martinovic J, Stanojlovic M, Sevigny J, Horvat A, Nedeljkovic N et al (2016) 17Beta-estradiol upregulates ecto-5′-nucleotidase (CD73) in hippocampal synaptosomes of female rats through action mediated by estrogen receptor-alpha and -beta. Neuroscience 324:286–296. https://doi.org/10.1016/j.neuroscience.2016.03.022

    Article  CAS  PubMed  Google Scholar 

  48. Brisevac D, Bjelobaba I, Bajic A, Clarner T, Stojiljkovic M, Beyer C, Andjus P, Kipp M et al (2012) Regulation of ecto-5′-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors. Neurochem Int 61(5):681–688. https://doi.org/10.1016/j.neuint.2012.06.017

    Article  CAS  PubMed  Google Scholar 

  49. Da Silva RS, Richetti SK, Tonial EM, Bogo MR, Bonan CD (2012) Profile of nucleotide catabolism and ectonucleotidase expression from the hippocampi of neonatal rats after caffeine exposure. Neurochem Res 37(1):23–30. https://doi.org/10.1007/s11064-011-0577-0

    Article  CAS  PubMed  Google Scholar 

  50. Mitrovic N, Gusevac I, Drakulic D, Stanojlovic M, Zlatkovic J, Sevigny J, Horvat A, Nedeljkovic N et al (2016) Regional and sex-related differences in modulating effects of female sex steroids on ecto-5′-nucleotidase expression in the rat cerebral cortex and hippocampus. Gen Comp Endocrinol 235:100–107. https://doi.org/10.1016/j.ygcen.2016.06.018

    Article  CAS  PubMed  Google Scholar 

  51. Milanese M, Bonifacino T, Zappettini S, Usai C, Tacchetti C, Nobile M, Bonanno G (2009) Glutamate release from astrocytic gliosomes under physiological and pathological conditions. Int Rev Neurobiol 85:295–318. https://doi.org/10.1016/S0074-7742(09)85021-6

    Article  CAS  PubMed  Google Scholar 

  52. Bari M, Bonifacino T, Milanese M, Spagnuolo P, Zappettini S, Battista N, Giribaldi F, Usai C et al (2011) The endocannabinoid system in rat gliosomes and its role in the modulation of glutamate release. Cell Mol Life Sci 68(5):833–845. https://doi.org/10.1007/s00018-010-0494-4

    Article  CAS  PubMed  Google Scholar 

  53. Corera AT, Doucet G, Fon EA (2009) Long-term potentiation in isolated dendritic spines. PLoS One 4(6):e6021. https://doi.org/10.1371/journal.pone.0006021

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Heine P, Braun N, Heilbronn A, Zimmermann H (1999) Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells. Eur J Biochem 262(1):102–107

    Article  CAS  PubMed  Google Scholar 

  55. Wink MR, Braganhol E, Tamajusuku AS, Casali EA, Karl J, Barreto-Chaves ML, Sarkis JJ, Battastini AM (2003) Extracellular adenine nucleotides metabolism in astrocyte cultures from different brain regions. Neurochem Int 43(7):621–628

    Article  CAS  PubMed  Google Scholar 

  56. Matyash M, Zabiegalov O, Wendt S, Matyash V, Kettenmann H (2017) The adenosine generating enzymes CD39/CD73 control microglial processes ramification in the mouse brain. PLoS One 12(4):e0175012. https://doi.org/10.1371/journal.pone.0175012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Vlajkovic SM, Housley GD, Greenwood D, Thorne PR (1999) Evidence for alternative splicing of ecto-ATPase associated with termination of purinergic transmission. Brain Res Mol Brain Res 73(1–2):85–92

    Article  CAS  PubMed  Google Scholar 

  58. Vlajkovic SM, Wang CJ, Soeller C, Zimmermann H, Thorne PR, Housley GD (2007) Activation-dependent trafficking of NTPDase2 in Chinese hamster ovary cells. Int J Biochem Cell Biol 39(4):810–817. https://doi.org/10.1016/j.biocel.2007.01.003

    Article  CAS  PubMed  Google Scholar 

  59. Wang CJ, Vlajkovic SM, Housley GD, Braun N, Zimmermann H, Robson SC, Sevigny J, Soeller C et al (2005) C-terminal splicing of NTPDase2 provides distinctive catalytic properties, cellular distribution and enzyme regulation. Biochem J 385(Pt 3):729–736. https://doi.org/10.1042/BJ20040852

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Hansen KR, Resta R, Webb CF, Thompson LF (1995) Isolation and characterization of the promoter of the human 5′-nucleotidase (CD73)-encoding gene. Gene 167(1–2):307–312

    Article  CAS  PubMed  Google Scholar 

  61. Spychala J, Lazarowski E, Ostapkowicz A, Ayscue LH, Jin A, Mitchell BS (2004) Role of estrogen receptor in the regulation of ecto-5′-nucleotidase and adenosine in breast cancer. Clin Cancer Res 10(2):708–717

    Article  CAS  PubMed  Google Scholar 

  62. Zelinski DP, Zantek ND, Walker-Daniels J, Peters MA, Taparowsky EJ, Kinch MS (2002) Estrogen and Myc negatively regulate expression of the EphA2 tyrosine kinase. J Cell Biochem 85(4):714–720. https://doi.org/10.1002/jcb.10186

    Article  CAS  PubMed  Google Scholar 

  63. Vivar OI, Zhao X, Saunier EF, Griffin C, Mayba OS, Tagliaferri M, Cohen I, Speed TP et al (2010) Estrogen receptor beta binds to and regulates three distinct classes of target genes. J Biol Chem 285(29):22059–22066. https://doi.org/10.1074/jbc.M110.114116

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Spychala J, Zimmermann AG, Mitchell BS (1999) Tissue-specific regulation of the ecto-5′-nucleotidase promoter. Role of the camp response element site in mediating repression by the upstream regulatory region. J Biol Chem 274(32):22705–22712

    Article  CAS  PubMed  Google Scholar 

  65. Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK et al (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38(11):1289–1297. https://doi.org/10.1038/ng1901

    Article  CAS  PubMed  Google Scholar 

  66. Spychala J, Mitchell BS, Barankiewicz J (1997) Adenosine metabolism during phorbol myristate acetate-mediated induction of HL-60 cell differentiation: changes in expression pattern of adenosine kinase, adenosine deaminase, and 5′-nucleotidase. J Immunol 158(10):4947–4952

    CAS  PubMed  Google Scholar 

  67. Milner TA, Ayoola K, Drake CT, Herrick SP, Tabori NE, McEwen BS, Warrier S, Alves SE (2005) Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation. J Comp Neurol 491(2):81–95. https://doi.org/10.1002/cne.20724

    Article  CAS  PubMed  Google Scholar 

  68. Bilbao PS, Katz S, Boland R (2012) Interaction of purinergic receptors with GPCRs, ion channels, tyrosine kinase and steroid hormone receptors orchestrates cell function. Purinergic Signal 8(1):91–103. https://doi.org/10.1007/s11302-011-9260-9

    Article  CAS  PubMed  Google Scholar 

  69. Campanac E, Gasselin C, Baude A, Rama S, Ankri N, Debanne D (2013) Enhanced intrinsic excitability in basket cells maintains excitatory-inhibitory balance in hippocampal circuits. Neuron 77(4):712–722. https://doi.org/10.1016/j.neuron.2012.12.020

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Terence Kirley from the University of Cincinnati, OH, USA, for a kind gift of rabbit anti-rat NTPDase2 and NTPDase3 antibodies used in this study.

Funding

The study was entirely supported by Ministry of Education, Science and Technological Development of the Republic of Serbia Nos. OI173044 and III41014.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ivana Grković.

Ethics declarations

All experimental procedures involving rats were approved by the Ethical Committee for the Use of Laboratory Animals of Vinča Institute of Nuclear Sciences, Belgrade, Republic of Serbia (Application No. 02/11) and carried out according to the European Communities Council Directive (2010/63/EU).

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Figure 1

Microglial cells in the stratum oriens, labeled with ATP enzyme histochemistry. (A) In control animals (Int), microglial cells exhibit typical small ovoid cell body with radially oriented ramified processes. (B) Removal of ovaries (OVX) induced visible changes the morphology of microglia, which became slightly enlarged and with a bipolar, lengthwise orientation of processes giving them the appearance of a less ramified cells. (C) Treatment with E2 restored highly ramified appearance similar to that found in control. Scale bar: 20 μm (PNG 1707 kb)

High Resolution Image (TIF 2160 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grković, I., Mitrović, N., Dragić, M. et al. Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement. Mol Neurobiol 56, 1933–1945 (2019). https://doi.org/10.1007/s12035-018-1217-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-018-1217-3

Keywords

Navigation