Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases

  • Guendalina Olivero
  • Matteo Vergassola
  • Francesca Cisani
  • Cesare Usai
  • Anna PittalugaEmail author


Mouse hippocampal glutamatergic nerve endings express presynaptic release-regulating NMDA autoreceptors (NMDARs). The presence of GluN1, GluN2A, GluN2B, and GluN3A subunits in hippocampal vesicular glutamate transporter type 1-positive synaptosomes was confirmed with confocal microscopy. GluN2C, GluN2D, and GluN3B immunopositivity was scarcely present. Incubation of synaptosomes with the anti-GluN1, the anti-GluN2A, the anti-GluN2B, or the anti-GluN3A antibody prevented the 30 μM NMDA/1 μM glycine-evoked [3H]d-aspartate ([3H]d-ASP) release. The NMDA/glycine-evoked [3H]d-ASP release was reduced by increasing the external protons, consistent with the participation of GluN1 subunits lacking the N1 cassette to the receptor assembly. The result also excludes the involvement of GluN1/GluN3A dimers into the NMDA-evoked overflow. Complement (1:300) released [3H]d-ASP in a dizocilpine-sensitive manner, suggesting the participation of a NMDAR-mediated component in the releasing activity. Accordingly, the complement-evoked glutamate overflow was reduced in anti-GluN-treated synaptosomes when compared to the control. We speculated that incubation with antibodies had favored the internalization of NMDA receptors. Indeed, a significant reduction of the GluN1 and GluN2B proteins in the plasma membranes of anti-GluN1 or anti-GluN2B antibody-treated synaptosomes emerged in biotinylation studies. Altogether, our findings confirm the existence of presynaptic GluN3A-containing release-regulating NMDARs in mouse hippocampal glutamatergic nerve endings. Furthermore, they unveil presynaptic alteration of the GluN subunit insertion in synaptosomal plasma membranes elicited by anti-GluN antibodies that might be relevant to the central alterations occurring in patients suffering from autoimmune anti-NMDA diseases.


Presynaptic NMDA autoreceptor GluN3 Anti-GluN antibody Complement NMDA internalization 



The authors thank Maura Agate and Silvia Smith, PhD (University of Utah, School of Medicine) for editorial assistance and Prof. Alberto Diaspro for the confocal microscope availability at the Department of Physics, University of Genova.

Funding Information

This work was supported by the University of Genoa (Fondi per la Ricerca di Ateneo).

Compliance with Ethical Standard

The experimental procedures were in accordance with the European legislation (European Communities Council Directive of 24 November 1986, 86/609/EEC) and the ARRIVE guidelines, and they were approved by the Italian Ministry of Health (DDL 26/2014 and previous legislation; protocol number no. 50/2011-B).

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Bouvier G, Bidoret C, Casado M, Paoletti P (2015) Presynaptic NMDA receptors: roles and rules. Neuroscience 311:322–340. CrossRefPubMedGoogle Scholar
  2. 2.
    Bouvier G, Larsen RS, Rodríguez-Moreno A, Paulsen O, Sjöström PJ (2018) Towards resolving the presynaptic NMDA receptor debate. Curr Opin Neurobiol 51:1–7. CrossRefPubMedGoogle Scholar
  3. 3.
    Banerjee A, Larsen RS, Philpot B, Paulsen O (2016) Roles of presynaptic NMDA receptors in neurotransmission and plasticity. Trends Neurosci 39:26–39. CrossRefPubMedGoogle Scholar
  4. 4.
    López-Colomé AM, Roberts PJ (1987) Effect of excitatory amino acid analogues on the release of D-[3H]aspartate from chick retina. Eur J Pharmacol 142:409–417. CrossRefPubMedGoogle Scholar
  5. 5.
    Desce JM, Godeheu G, Galli T, Artaud F, Chéramy A, Glowinski J (1992) L-glutamate-evoked release of dopamine from synaptosomes of the rat striatum: involvement of AMPA and N-methyl-D-aspartate receptors. Neuroscience 47:333–339. CrossRefPubMedGoogle Scholar
  6. 6.
    Malva JO, Carvalho AP, Carvalho CM (1994) Modulation of dopamine and noradrenaline release and of intracellular Ca2+ concentration by presynaptic glutamate receptors in hippocampus. Br J Pharmacol 113:1439–1447. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pittaluga A, Pattarini R, Feligioni M, Raiteri M (2001) N-methyl-D-aspartate receptors mediating hippocampal noradrenaline and striatal dopamine release display differential sensitivity to quinolinic acid, the HIV-1 envelope protein gp120, external pH and protein kinase C inhibition. J Neurochem 76:139–148. CrossRefPubMedGoogle Scholar
  8. 8.
    Salamone A, Zappettini S, Grilli M, Olivero G, Agostinho P, Tomè AR, Chen J, Pittaluga A et al (2014) Prolonged nicotine exposure down-regulates presynaptic NMDA receptors in dopaminergic terminals of the rat nucleus accumbens. Neuropharmacology 79:488–497. CrossRefPubMedGoogle Scholar
  9. 9.
    Zappettini S, Grilli M, Olivero G, Chen J, Padolecchia C, Pittaluga A, Tomé AR, Cunha RA et al (2014) Nicotinic α7 receptor activation selectively potentiates the function of NMDA receptors in glutamatergic terminals of the nucleus accumbens. Front Cell Neurosci 8:332. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fink K, Göthert M, Molderings G, Schlicker E (1989) N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of noradrenaline release, but not release of other neurotransmitters, in the rat brain cortex: receptor location, characterization and desensitization. Naunyn Schmiedeberg's Arch Pharmacol 339:514–521 Erratum in: Naunyn Schmiedeberg's Arch Pharmacol 340:595. 10.1007/BF00167254CrossRefGoogle Scholar
  11. 11.
    Pittaluga A, Raiteri M (1990) Release-enhancing glycine-dependent presynaptic NMDA receptors exist on noradrenergic terminals of hippocampus. Eur J Pharmacol 191:231–234. CrossRefPubMedGoogle Scholar
  12. 12.
    Pittaluga A, Raiteri M (1992) N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. I. Location on axon terminals and pharmacological characterization. J Pharmacol Exp Ther 260:232–237PubMedGoogle Scholar
  13. 13.
    Wang JK, Andrews H, Thukral V (1992) Presynaptic glutamate receptors regulate noradrenaline release from isolated nerve terminals. J Neurochem 58:204–211. CrossRefPubMedGoogle Scholar
  14. 14.
    Luccini E, Musante V, Neri E, Brambilla Bas M, Severi P, Raiteri M, Pittaluga A (2007a) Functional interactions between presynaptic NMDA receptors and metabotropic glutamate receptors co-expressed on rat and human noradrenergic terminals. Br J Pharmacol 151:1087–1094. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Grilli M, Zappettini S, Zanardi A, Lagomarsino F, Pittaluga A, Zoli M, Marchi M (2009) Exposure to an enriched environment selectively increases the functional response of the pre-synaptic NMDA receptors which modulate noradrenaline release in mouse hippocampus. J Neurochem 110:1598–1606. CrossRefPubMedGoogle Scholar
  16. 16.
    Paudice P, Gemignani A, Raiteri M (1998) Evidence for functional native NMDA receptors activated by glycine or D-serine alone in the absence of glutamatergic coagonist. Eur J Neurosci 10:2934–2944. CrossRefPubMedGoogle Scholar
  17. 17.
    Gemignani A, Paudice P, Pittaluga A, Raiteri M (2000) The HIV-1 coat protein gp120 and some of its fragments potently activate native cerebral NMDA receptors mediating neuropeptide release. Eur J Neurosci 12:2839–2846. CrossRefPubMedGoogle Scholar
  18. 18.
    Morari M, Sbrenna S, Marti M, Caliari F, Bianchi C, Beani L (1998) NMDA and non-NMDA ionotropic glutamate receptors modulate striatal acetylcholine release via pre- and postsynaptic mechanisms. J Neurochem 71:2006–2017. CrossRefPubMedGoogle Scholar
  19. 19.
    Duguid IC, Smart TG (2004) Retrograde activation of presynaptic NMDARs enhances GABA release at cerebellar interneuron-Purkinje cell synapses. Nat Neurosci 7:525–533. CrossRefPubMedGoogle Scholar
  20. 20.
    Liu SJ, Lachamp P (2006) The activation of excitatory glutamate receptors evokes a long-lasting increase in the release of GABA from cerebellar stellate cells. J Neurosci 26:9332–9339. CrossRefPubMedGoogle Scholar
  21. 21.
    Martin D, Bustos GA, Bowe MA, Bray SD, Nadler JV (1991) Autoreceptor regulation of glutamate and aspartate release from slices of the hippocampal CA1 area. J Neurochem 56:1647–1655. CrossRefPubMedGoogle Scholar
  22. 22.
    Breukel AI, Besselsen E, Lopes da Silva FH, Ghijsen WE (1998) A presynaptic N-methyl-D-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool. Eur J Neurosci 10:106–114. CrossRefPubMedGoogle Scholar
  23. 23.
    Luccini E, Musante V, Neri E, Raiteri M, Pittaluga A (2007b) N-methyl-D-aspartate autoreceptors respond to low and high agonist concentrations by facilitating, respectively, exocytosis and carrier-mediated release of glutamate in rat hippocampus. J Neurosci Res 85:3657–3665. CrossRefPubMedGoogle Scholar
  24. 24.
    Musante V, Summa M, Cunha RA, Raiteri M, Pittaluga A (2011) Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions. J Neurochem 117:516–527. CrossRefPubMedGoogle Scholar
  25. 25.
    Summa M, Di Prisco S, Grilli M, Marchi M, Pittaluga A (2011) Hippocampal AMPA autoreceptors positively coupled to NMDA autoreceptors traffic in a constitutive manner and undergo adaptative changes following enriched environment training. Neuropharmacology 61:1282–1290. CrossRefPubMedGoogle Scholar
  26. 26.
    Paoletti P, Bellone C, Zhou Q (2013) NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci 14(6):383–400. CrossRefPubMedGoogle Scholar
  27. 27.
    Pérez-Otaño I, Larsen RS, Wesseling JF (2016) Emerging roles of GluN3-containing NMDA receptors in the CNS. Nat Rev Neurosci 17(10):623–635. CrossRefPubMedGoogle Scholar
  28. 28.
    Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 5(2):160–170. CrossRefPubMedGoogle Scholar
  29. 29.
    Burnell ES, Irvine M, Fang G, Sapkota K, Jane DE, Monaghan DT (2018) Positive and negative allosteric modulators of N-methyl-d-aspartate (NMDA) receptors: structure-activity relationships and mechanisms of action. J Med Chem.
  30. 30.
    Larsen RS, Corlew RJ, Henson MA, Roberts AC, Mishina M, Watanabe M, Lipton SA, Nakanishi N et al (2011) NR3A-containing NMDARs promote neurotransmitter release and spike timing-dependent plasticity. Nat Neurosci 14(3):338–344. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Gupta A, Heimann AS, Gomes I, Devi LA (2008) Antibodies against G-protein coupled receptors: novel uses in screening and drug development. Comb Chem High Throughput Screen 11:463–467. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Musante V, Longordo F, Neri E, Pedrazzi M, Kalfas F, Severi P, Raiteri M, Pittaluga A (2008a) RANTES modulates the release of glutamate in human neocortex. J Neurosci 28:12231–12240. CrossRefPubMedGoogle Scholar
  33. 33.
    Di Prisco S, Summa M, Chellackudam V, Rossi PI, Pittaluga A (2012) RANTES-mediated control of excitatory amino acid release in mouse spinal cord. J Neurochem 121:428–437. CrossRefPubMedGoogle Scholar
  34. 34.
    Olivero G, Bonfiglio T, Vergassola M, Usai C, Riozzi B, Battaglia G, Nicoletti F, Pittaluga A (2017) Immuno-pharmacological characterization of group II metabotropic glutamate receptors controlling glutamate exocytosis in mouse cortex and spinal cord. Br J Pharmacol 174:4785–4796. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Scholler P, Nevoltris D, de Bundel D, Bossi S, Moreno-Delgado D, Rovira X, Møller TC, El Moustaine D, Mathieu M, Blanc E, McLean H, Dupuis E, Mathis G, Trinquet E, Daniel H, Valjent E, Baty D, Chames P, Rondard P, Pin JP (2017) Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nat Commun 8:1967., 1967
  36. 36.
    Summa M, Di Prisco S, Grilli M, Usai C, Marchi M, Pittaluga A (2013) Presynaptic mGlu7 receptors control GABA release in mouse hippocampus. Neuropharmacology 66:215–224. CrossRefPubMedGoogle Scholar
  37. 37.
    Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25:411–414. CrossRefPubMedGoogle Scholar
  38. 38.
    Pittaluga A (2016) Presynaptic release-regulating mGlu1 receptors in central nervous system. Front Pharmacol 7:295. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zucchini S, Pittaluga A, Brocca-Cofano E, Summa M, Fabris M, De Michele R, Bonaccorsi A, Busatto G et al (2013) Increased excitability in tat-transgenic mice: role of tat in HIV-related neurological disorders. Neurobiol Dis 55:110–119. CrossRefPubMedGoogle Scholar
  40. 40.
    Musante V, Neri E, Feligioni M, Puliti A, Pedrazzi M, Conti V, Usai C, Diaspro A et al (2008b) Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from mouse cortical nerve endings. Neuropharmacology 55:474–482. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Manders EMM, Verbeek FJ, Aten JA (1993) Measurement of colocalization of objects in dual-colour confocal images. J Microsc 169:375–382. CrossRefGoogle Scholar
  42. 42.
    Gonzalez RC, Wintz P (1987) Digital image processing, 2nd ed. Addison Wesley Publication Company, MassGoogle Scholar
  43. 43.
    Costes SV, Daelemans D, Cho EH, Dobbin Z, Pavlakis G, Lockett S (2004) Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys J 86:3993–4003. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B et al (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256(5060):1217–1212. CrossRefPubMedGoogle Scholar
  45. 45.
    Dubois CJ, Lachamp PM, Sun L, Mishina M, Liu SJ (2016) Presynaptic GluN2D receptors detect glutamate spillover and regulate cerebellar GABA release. J Neurophysiol 115(1):271–285. CrossRefPubMedGoogle Scholar
  46. 46.
    Ravikrishnan A, Gandhi PJ, Shelkar GP, Liu J, Pavuluri R, Dravid SM (2018) Region-specific expression of NMDA receptor GluN2C subunit in parvalbumin-positive neurons and astrocytes: analysis of GluN2C expression using a novel reporter model. Neurosci;380:49–62.
  47. 47.
    Sibarov DA, Stepanenko YD, Silantiev IV, Abushik PA, Karelina TV, Antonov SM (2018) Developmental changes of synaptic and extrasynaptic NMDA receptor expression in rat cerebellar neurons in vitro. J Mol Neurosci 64(2):300–311. CrossRefPubMedGoogle Scholar
  48. 48.
    Wong HK, Liu XB, Matos MF, Chan SF, Pérez-Otaño I, Boysen M, Cui J, Nakanishi N et al (2002) Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain. J Comp Neurol 450(4):303–317. CrossRefPubMedGoogle Scholar
  49. 49.
    Henson MA, Larsen RS, Lawson SN, Pérez-Otaño I, Nakanishi N, Lipton SA, Philpot BD (2012) Genetic deletion of NR3A accelerates glutamatergic synapse maturation. PLoS One 7(8):e42327. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Grilli M, Raiteri L, Pittaluga A (2004) Somatostatin inhibits glutamate release from mouse cerebrocortical nerve endings through presynaptic sst2 receptors linked to the adenylyl cyclase-protein kinase a pathway. Neuropharmacology 46:388–396. CrossRefPubMedGoogle Scholar
  51. 51.
    Zukin RS, Bennett MV (1995) Alternatively spliced isoforms of the NMDARI receptor subunit. Trends Neurosci 18(7):306–313. CrossRefPubMedGoogle Scholar
  52. 52.
    Perez-Otano I, Schulteis CT, Contractor A, Lipton SA, Trimmer JS, Sucher NJ, Heinemann SF (2001) Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J Neurosci 21(4):1228–1237. CrossRefPubMedGoogle Scholar
  53. 53.
    Cummings KA, Popescu GK (2015) Glycine-dependent activation of NMDA receptors. J Gen Physiol 145(6):513–527. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Merega E, Di Prisco S, Lanfranco M, Severi P, Pittaluga A (2014) Complement selectively elicits glutamate release from nerve endings in different regions of mammal central nervous system. J Neurochem 129:473–483. CrossRefPubMedGoogle Scholar
  55. 55.
    Merega E, Prisco SD, Severi P, Kalfas F, Pittaluga A (2015) Antibody/receptor protein immunocomplex in human and mouse cortical nerve endings amplifies complement-induced glutamate release. Neurosci Lett 600:50–55. CrossRefPubMedGoogle Scholar
  56. 56.
    Dalmau J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: The 2016 Cotzias Lecture. Neurology 87:2471–2482. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Fukata M, Yokoi N, Fukata Y (2018) Neurobiology of autoimmune encephalitis. Curr Opin Neurobiol 48:1–8. CrossRefPubMedGoogle Scholar
  58. 58.
    Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR et al (2010) Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 30(17):5866–5875. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhang Q, Tanaka K, Sun P, Nakata M, Yamamoto R, Sakimura K, Matsui M, Kato N (2012) Suppression of synaptic plasticity by cerebrospinal fluid from anti-NMDA receptor encephalitis patients. Neurobiol Dis 45:610–615. CrossRefPubMedGoogle Scholar
  60. 60.
    Moscato EH, Peng X, Jain A, Parsons TD, Dalmau J, Balice-Gordon RJ (2014) Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 76:108–119. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kreye J, Wenke NK, Chayka M, Leubner J, Murugan R, Maier N, Jurek B, Ly LT et al (2016) Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain 139:2641–2652. CrossRefPubMedGoogle Scholar
  62. 62.
    Rodríguez-Moreno A, Banerjee A, Paulsen O (2010) Presynaptic NMDA receptors and spike timing-dependent depression at cortical synapses. Front Synaptic Neurosci 2:18. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Duguid IC (2013) Presynaptic NMDA receptors: are they dendritic receptors in disguise? Brain Res Bull 93:4–9. CrossRefPubMedGoogle Scholar
  64. 64.
    Berg LK, Larsson M, Morland C, Gundersen V (2013) Pre and postsynaptic localization of NMDA receptor subunits at hippocampal mossy fibre synapses. Neurosci 230:139–150. CrossRefGoogle Scholar
  65. 65.
    Stanic J, Carta M, Eberini I, Pelucchi S, Marcello E, Genazzani AA, Racca C, Mulle C et al (2015) Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex. Nat Commun 6:10181. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Chowdhury D, Marco S, Brooks IM, Zandueta A, Rao Y, Haucke V, Wesseling JF, Tavalin SJ et al (2013) Tyrosine phosphorylation regulates the endocytosis and surface expression of GluN3A-containing NMDA receptors. J Neurosci 33(9):4151–4164. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Andrade-Talavera Y, Duque-Feria P, Paulsen O, Rodríguez-Moreno A (2016) Presynaptic spike timing-dependent long-term depression in the mouse hippocampus. Cereb Cortex 26(8):3637–3654. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S et al (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415(6873):793–798. CrossRefPubMedGoogle Scholar
  69. 69.
    Di Prisco S, Olivero G, Merega E, Bonfiglio T, Marchi M, Pittaluga A (2016) CXCR4 and NMDA receptors are functionally coupled in rat hippocampal noradrenergic and glutamatergic nerve endings. J NeuroImmune Pharmacol 11(4):645–656. CrossRefPubMedGoogle Scholar
  70. 70.
    Stroebel D, Casado M, Paoletti P (2017) Triheteromeric NMDA receptors: From structure to synaptic physiology. Curr Opin Physiol 2:1–12. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Stys PK, Lipton SA (2007) White matter NMDA receptors: an unexpected new therapeutic target? Trends Pharmacol Sci 28(11):561–566. CrossRefPubMedGoogle Scholar
  72. 72.
    Kehoe LA, Bernardinelli Y, Muller D (2013) GluN3A: an NMDA receptor subunit with exquisite properties and functions. Neural Plast 2013:145387. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Masdeu JC, Dalmau J, Berman KF (2016) NMDA receptor internalization by autoantibodies: a reversible mechanism underlying psychosis? Trends Neurosci 39:300–310. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Jézéquel J, Johansson EM, Dupuis JP, Rogemond V, Gréa H, Kellermayer B (2017) Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients. Nat Commun 8(1):1791. CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Pharmacy, DiFAR, Pharmacology and Toxicology SectionUniversity of GenoaGenoaItaly
  2. 2. Institute of Biophysics, National Research CouncilGenoaItaly
  3. 3.IRCCS Ospedale Policlinico San MartinoGenovaItaly

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