Advertisement

Journal of Neural Transmission

, Volume 124, Issue 3, pp 273–284 | Cite as

Higher levels of different muscarinic receptors in the cortex and hippocampus from subjects with Alzheimer’s disease

  • Elizabeth Scarr
  • Catriona McLean
  • Brian Dean
Neurology and Preclinical Neurological Studies - Original Article

Abstract

It has been suggest that drugs specifically targeting muscarinic receptors will be useful in treating Alzheimer’s disease. We decided to determine if the response to such drugs may be altered, because of changes in the levels of muscarinic receptors in the CNS from subjects with the disorder. We used in situ radioligand binding with autoradiography to measure the levels of [3H]pirenzepine binding to muscarinic M1 receptors, [3H]AF-DX 386 binding to muscarinic M1, M2, and M4 receptors, and [3H]4-DAMP binding to muscarinic M1 and M3 receptors in the dorsolateral prefrontal cortex and hippocampus from subjects with Alzheimer’s and age/sex-matched controls. Compared with controls, [3H]pirenzepine binding was higher in the dentate gyrus from subjects with Alzheimer’s disease. [3H]AF-DX 386 binding was higher in the subiculum and parahippocampal gyrus from subjects with the disorder. In Alzheimer’s disease, [3H]-DAMP binding was higher in the dorsolateral prefrontal cortex but not different in the hippocampus. Our data show complex changes in the levels of muscarinic receptors in the CNS from subjects with Alzheimer’s disease which may affect clinical response to treatment with drugs-targeting these receptors.

Keywords

Alzheimer’s disease Cortex Hippocampus Muscarinic receptors 

Notes

Acknowledgments

The authors would like to thank Dr. Simone Boer and Ms. Susan Juzva for their excellent technical assistance. This work was supported in part by the National Medical and Health Research Council (Project Grant 566967: ES and BD; Senior Research Fellowship #APP1002240: BD), the Australian Research Council (Future Fellowship FT100100689: ES), and the Operational Infrastructure Support (OIS) from the Victorian State Government.

References

  1. Araujo DM, Lapchak PA, Robitaille Y, Gauthier S, Quirion R (1988) Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer’s disease. J Neurochem 50:1914–1923CrossRefPubMedGoogle Scholar
  2. Aubert I, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R (1992) Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer’s and Parkinson’s diseases. J Neurochem 58:529–541CrossRefPubMedGoogle Scholar
  3. Bodick NC, Offen WW, Levey AI, Cutler NR, Gauthier SG, Satlin A, Shannon HE, Tollefson GD, Rasmussen K, Bymaster FP, Hurley DJ, Potter WZ, Paul SM (1997) Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 54:465–473CrossRefPubMedGoogle Scholar
  4. Bolden C, Cusack B, Richelson E (1992) Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther 260:576–580PubMedGoogle Scholar
  5. Boundy KL, Barnden LR, Katsifis AG, Rowe CC (2005) Reduced posterior cingulate binding of I-123 iodo-dexetimide to muscarinic receptors in mild Alzheimer’s disease. J Clin Neurosci 12:421–425CrossRefPubMedGoogle Scholar
  6. Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16:271–278CrossRefPubMedGoogle Scholar
  7. Caulfield MP, Straughan DW, Cross AJ, Crow T, Birdsall NJ (1982) Cortical muscarinic receptor subtypes and Alzheimer’s disease. Lancet 2:1277CrossRefPubMedGoogle Scholar
  8. Colloby SJ, McKeith IG, Wyper DJ, O’Brien JT, Taylor J-P (2015) Regional covariance of muscarinic acetylcholine receptors in Alzheimer’s disease using (R, R) [123I]-QNB SPECT. J Neurol 262:2144–2153CrossRefPubMedGoogle Scholar
  9. Conn PJ, Jones CK, Lindsley CW (2009) Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. TIPS 30:148–155PubMedPubMedCentralGoogle Scholar
  10. Cook RD, Weisberg S (1999) Applied regression including computing and graphics. Wiley, HobokenCrossRefGoogle Scholar
  11. Crook JM, Dean B, Pavey G, Copolov D (1999) The binding of [3H]AF-DX 384 is reduced in the caudate-putamen of subjects with schizophrenia. Life Sci 64:1761–1771CrossRefPubMedGoogle Scholar
  12. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2000) Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation. Biol Psychiatry 48:381–388CrossRefPubMedGoogle Scholar
  13. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2001) Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann’s areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment. Am J Psychiatry 158:918–925CrossRefPubMedGoogle Scholar
  14. D’Agostino RB, Belanger A, D’Agostino Jnr RB (1990) A suggestion for using powerful and informative tests of normality. Am Stat 44:316–321Google Scholar
  15. Dean B (2012) Selective activation of muscarinic acetylcholine receptors for the treatment of schizophrenia. Curr Pharm Biotechnol 13:1563–1571CrossRefPubMedGoogle Scholar
  16. Dean B, Crook JM (1996) Muscarinic M1 receptors in schizophrenia. Mol Psychiatry 1:364–366Google Scholar
  17. Dean B, Crook JM, Opeskin K, Hill C, Keks N, Copolov DL (1996) The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia. Mol Psychiatry 1:54–58PubMedGoogle Scholar
  18. Dean B, Pavey G, Chai SY, Mendelsohn FAO (1999) The localisation and quantification of molecular changes in the human brain using in situ radioligand binding and autoradiography. In: Dean B, Kleinman JE, Hyde TM (eds) Using CNS tissue in psychiatric research: a practical guide. Harwood Academic Press, Amsterdam, pp 67–83CrossRefGoogle Scholar
  19. Dean B, Soulby A, Evin GM, Scarr E (2008) Levels of [(3)H]pirenzepine binding in Brodmann’s area 6 from subjects with schizophrenia is not associated with changes in the transcription factor SP1 or BACE1. Schizophr Res 106:229–236CrossRefPubMedGoogle Scholar
  20. Dean B, Hopper S, Conn PJ, Scarr E (2016) Changes in BQCA allosteric modulation of [3H]NMS binding to human cortex within schizophrenia and by divalent cations. Neuropsychopharmaclogy 41:1620–1628CrossRefGoogle Scholar
  21. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR (1991) Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther 256:727–733PubMedGoogle Scholar
  22. El Haj M, Antoine P, Amouyel P, Lambert JC, Pasquier F, Kapogiannis D (2016) Apolipoprotein E (APOE) epsilon4 and episodic memory decline in Alzheimer’s disease: a review. Ageing Res Rev 27:15–22CrossRefPubMedGoogle Scholar
  23. Ferrer I, Santpere G, Arzberger T, Bell J, Blanco R, Boluda S, Budka H, Carmona M, Giaccone G, Krebs B, Limido L, Parchi P, Puig B, Strammiello R, Strobel T, Kretzschmar H (2007) Brain protein preservation largely depends on the postmortem storage temperature: implications for study of proteins in human neurologic diseases and management of brain banks: a BrainNet Europe Study. J Neuropathol Exp Neurol 66:35–46CrossRefPubMedGoogle Scholar
  24. Fisher A, Heldman E, Gurwitz D, Haring R, Karton Y, Meshulam H, Pittel Z, Marciano D, Brandeis R, Sadot E, Barg Y, Pinkas-Kramarski R, Vogel Z, Ginzburg I, Treves TA, Verchovsky R, Klimowsky S, Korczyn AD (1996) M1 agonists for the treatment of Alzheimer’s disease. Novel properties and clinical update. Ann N Y Acad Sci 777:189–196CrossRefPubMedGoogle Scholar
  25. Flynn DD, Weinstein DA, Mash DC (1991) Loss of high-affinity agonist binding to M1 muscarinic receptors in Alzheimer’s disease: implications for the failure of cholinergic replacement therapies. Ann Neurol 29:256–262CrossRefPubMedGoogle Scholar
  26. Flynn DD, Ferrari-Dileo G, Mash DC, Levey AI (1995) Differential regulation of molecular subtypes of muscarinic receptors in Alzheimer’s disease. J Neurochem 64:1888–1891CrossRefPubMedGoogle Scholar
  27. Garey LJ (1994) Bordmann’s ‘Localisation in the cerebral cortex’. Smith-Gordon, LondonGoogle Scholar
  28. Gibbons A, Dean B (2016) The cholinergic system: an emerging drug target for schizophrenia. Curr Pharm Des 22:2124–2133CrossRefPubMedGoogle Scholar
  29. Gibbons AS, Scarr E, McLean C, Sundram S, Dean B (2009) Decreased muscarinic receptor binding in the frontal cortex of bipolar disorder and major depressive disorder subjects. J Affect Disord 116:184–191CrossRefPubMedGoogle Scholar
  30. Gibbons AS, Scarr E, Boer S, Money T, Jeon WJ, Felder C, Dean B (2013) Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia. Int J Neuropsychopharmacol 16:37–46CrossRefPubMedGoogle Scholar
  31. Harrison PJ, Barton AJ, Najlerahim A, McDonald B, Pearson RC (1991) Increased muscarinic receptor messenger RNA in Alzheimer’s disease temporal cortex demonstrated by in situ hybridization histochemistry. Brain Res Mol Brain Res 9(1–2):15–21CrossRefPubMedGoogle Scholar
  32. Holman BL, Gibson RE, Hill TC, Eckelman WC, Albert M, Reba RC (1985) Muscarinic acetylcholine receptors in Alzheimer’s disease. In vivo imaging with iodine 123-labeled 3-quinuclidinyl-4-iodobenzilate and emission tomography. JAMA 254:3063–3066CrossRefPubMedGoogle Scholar
  33. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 8:1–13CrossRefPubMedPubMedCentralGoogle Scholar
  34. Jeon WJ, Gibbons AS, Dean B (2013) The use of a modified [3H]4-DAMP radioligand binding assay with increased selectivity for muscarinic M3 receptor shows that cortical CHRM3 levels are not altered in mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 47:7–12CrossRefPubMedGoogle Scholar
  35. Jositsch G, Papadakis T, Haberberger RV, Wolff M, Wess J, Kummer W (2009) Suitability of muscarinic acetylcholine receptor antibodies for immunohistochemistry evaluated on tissue sections of receptor gene-deficient mice. Naunyn Schmiedebergs Arch Pharmacol 379:389–395CrossRefPubMedGoogle Scholar
  36. Kar S, Slowikowski SPM, Westaway D, Mount HTJ (2004) Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. J Psychiatry Neurosci 29:427–441PubMedPubMedCentralGoogle Scholar
  37. Keihan FS, Roßner S, Ghafari M, Groessl M, Morawski M, Gerner C, Lubec G (2014) Changes of several brain receptor complexes in the cerebral cortex of patients with Alzheimer disease: probable new potential pharmaceutical targets. Amino Acids 46:223–233. doi: 10.1007/s00726-013-1623-9 CrossRefGoogle Scholar
  38. Kellar KJ, Whitehouse PJ, Martino-Barrows AM, Marcus K, Price DL (1987) Muscarinic and nicotinic cholinergic binding sites in Alzheimer’s disease cerebral cortex. Brain Res 436:62–68CrossRefPubMedGoogle Scholar
  39. Kemp PM, Holmes C, Hoffmann S, Wilkinson S, Zivanovic M, Thom J, Bolt L, Fleming J, Wilkinson DG (2003) A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 74:1567–1570CrossRefPubMedPubMedCentralGoogle Scholar
  40. Kim HK, Nunes PV, Oliveira KC, Young LT, Lafer B (2016) Neuropathological relationship between major depression and dementia: a hypothetical model and review. Prog Neuropsychopharmacol Biol Psychiatry 67:51–57CrossRefPubMedGoogle Scholar
  41. Kingsbury AE, Foster OJ, Nisbet AP, Cairns N, Bray L, Eve DJ, Lees AJ, Marsden CD (1995) Tissue pH as an indicator of mRNA preservation in human post-mortem brain. Brain Res Mol Brain Res 28:311–318CrossRefPubMedGoogle Scholar
  42. Ladner CJ, Lee JM (1999) Reduced high-affinity agonist binding at the M(1) muscarinic receptor in Alzheimer’s disease brain: differential sensitivity to agonists and divalent cations. Exp Neurol 158:451–458CrossRefPubMedGoogle Scholar
  43. Ladner CJ, Celesia GG, Magnuson DJ, Lee JM (1995) Regional alterations in M1 muscarinic receptor-G protein coupling in Alzheimer’s disease. J Neuropathol Exp Neurol 54:783–789CrossRefPubMedGoogle Scholar
  44. Lange KW, Wells FR, Rossor MN, Jenner P, Marsden CD (1989) Brain muscarinic receptors in Alzheimer’s and Parkinson’s diseases. Lancet 2:1279CrossRefPubMedGoogle Scholar
  45. Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer’s disease and experimental cholinergic denervation. Science 228:1115–1117CrossRefPubMedGoogle Scholar
  46. Miller JH, Gibson VA, McKinney M (1991) Binding of [3H]AF-DX 384 to cloned and native muscarinic receptors. J Pharmacol Exp Ther 259:601–607PubMedGoogle Scholar
  47. Mulugeta E, Karlsson E, Islam A, Kalaria R, Mangat H, Winblad B, Adem A (2003) Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients. Brain Res 960:259–262CrossRefPubMedGoogle Scholar
  48. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258:304–307CrossRefPubMedGoogle Scholar
  49. Nordberg A, Alafuzoff I, Winblad B (1986) Muscarinic receptor subtypes in hippocampus in Alzheimer’s disease and mixed dementia type. Neurosci Lett 70:160–164CrossRefPubMedGoogle Scholar
  50. Overk CR, Felder CC, Tu Y, Schober DA, Bales KR, Wuu J, Mufson EJ (2010) Cortical M1 receptor concentration increases without a concomitant change in function in Alzheimer’s disease. J Chem Neuroanat 40:63–70CrossRefPubMedPubMedCentralGoogle Scholar
  51. Pakrasi S, Colloby SJ, Firbank MJ, Perry EK, Wyper DJ, Owens J, McKeith IG, Williams ED, O’Brien JT (2007) Muscarinic acetylcholine receptor status in Alzheimer’s disease assessed using (R, R) 123I-QNB SPECT. J Neurol 254:907–913CrossRefPubMedGoogle Scholar
  52. Pavey GM, Copolov DL, Dean B (2002) High-resolution phosphor imaging: validation for use with human brain tissue sections to determine the affinity and density of radioligand binding. J Neurosci Methods 116:157–163CrossRefPubMedGoogle Scholar
  53. Perry E, Walker M, Grace J, Perry R (1999) Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci 22:273–280CrossRefPubMedGoogle Scholar
  54. Piggott MA, Owens J, O’Brien J, Colloby S, Fenwick J, Wyper D, Jaros E, Johnson M, Perry RH, Perry EK (2003) Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease. J Chem Neuroanat 25:161–173CrossRefPubMedGoogle Scholar
  55. Potter PE, Rauschkolb PK, Pandya Y, Sue LI, Sabbagh MN, Walker DG, Beach TG (2011) Pre- and post-synaptic cortical cholinergic deficits are proportional to amyloid plaque presence and density at preclinical stages of Alzheimer’s disease. Acta Neuropathol 122:49–60CrossRefPubMedPubMedCentralGoogle Scholar
  56. Reinikainen KJ, Riekkinen PJ, Halonen T, Laakso M (1987) Decreased muscarinic receptor binding in cerebral cortex and hippocampus in Alzheimer’s disease. Life Sci 41:453–461CrossRefPubMedGoogle Scholar
  57. Rinne JO, Lonnberg P, Marjamaki P, Rinne UK (1989) Brain muscarinic receptor subtypes are differently affected in Alzheimer’s disease and Parkinson’s disease. Brain Res 483:402–406CrossRefPubMedGoogle Scholar
  58. Rodbard D (1981) Mathematics and statistics of ligand assays: An illustrated guide. In: Langan J, Clapp JJ (eds) Ligand Assay: Analysis of international developments on isotopic and nonisotopic immunoassay. Masson Punlishing USA Inc, New York, pp 45–99Google Scholar
  59. Rodriguez-Puertas R, Pascual J, Vilaro T, Pazos A (1997) Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer’s disease. Synapse 26:341–350CrossRefPubMedGoogle Scholar
  60. Scarr E, Dean B (2008) Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia? J Neurochem 107:1188–1195CrossRefPubMedGoogle Scholar
  61. Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B (2009) Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol Psychiatry 14:1017–1023CrossRefPubMedGoogle Scholar
  62. Scarr E, Gibbons AS, Neo J, Udawela M, Dean B (2013) Cholinergic connectivity: it’s implications for psychiatric disorders. Front Cell Neurosci. doi: 10.3389/fncel.2013.0055 PubMedPubMedCentralGoogle Scholar
  63. Stan AD, Ghose S, Gao XM, Roberts RC, Lewis-Amezcua K, Hatanpaa KJ, Tamminga CA (2006) Human postmortem tissue: what quality markers matter? Brain Res 1123:1–11CrossRefPubMedPubMedCentralGoogle Scholar
  64. Svensson AL, Warpman U, Hellstrom-Lindahl E, Bogdanovic N, Lannfelt L, Nordberg A (1997) Nicotinic receptors, muscarinic receptors and choline acetyltransferase activity in the temporal cortex of Alzheimer patients with differing apolipoprotein E genotypes. Neurosci Lett 232:37–40CrossRefPubMedGoogle Scholar
  65. Tsang SW, Lai MK, Kirvell S, Francis PT, Esiri MM, Hope T, Chen CP, Wong PT (2006) Impaired coupling of muscarinic M1 receptors to G-proteins in the neocortex is associated with severity of dementia in Alzheimer’s disease. Neurobiol Aging 27:1216–1223CrossRefPubMedGoogle Scholar
  66. Tsang SW, Pomakian J, Marshall GA, Vinters HV, Cummings JL, Chen CP, Wong PT, Lai MK (2007) Disrupted muscarinic M1 receptor signaling correlates with loss of protein kinase C activity and glutamatergic deficit in Alzheimer’s disease. Neurobiol Aging 28:1381–1387CrossRefPubMedGoogle Scholar
  67. Tsang SW, Francis PT, Esiri MM, Wong PT, Chen CP, Lai MK (2008) Loss of [3H]4-DAMP binding to muscarinic receptors in the orbitofrontal cortex of Alzheimer’s disease patients with psychosis. Psychopharmacol (Berlin) 198:251–259CrossRefGoogle Scholar
  68. van Strien NM, Cappaert NL, Witter MP (2009) The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci 10:272–282CrossRefPubMedGoogle Scholar
  69. Vanderheyden P, Ebinger G, Dierckx R, Vauquelin G (1987) Muscarinic cholinergic receptor subtypes in normal human brain and Alzheimer’s presenile dementia. J Neurol Sci 82:257–269CrossRefPubMedGoogle Scholar
  70. Vogt BA, Crino PB, Volicer L (1991) Laminar alterations in gamma-aminobutyric acid, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer’s disease. J Neurochem 57:282–290CrossRefPubMedGoogle Scholar
  71. Waller SB, Ball MJ, Reynolds MA, London ED (1986) Muscarinic binding and choline acetyltransferase in postmortem brains of demented patients. Can J Neurol Sci 13(Suppl):528–532CrossRefPubMedGoogle Scholar
  72. Wang SZ, Zhu SZ, Mash DC, el-Fakahany EE (1992) Comparison of the concentration of messenger RNA encoding four muscarinic receptor subtypes in control and Alzheimer brains. Brain Res Mol Brain Res 16(1–2):64–70CrossRefPubMedGoogle Scholar
  73. Warren NM, Piggott MA, Lees AJ, Perry EK, Burn DJ (2008) Intact coupling of M1 receptors and preserved M2 and M4 receptors in the cortex in progressive supranuclear palsy: contrast with other dementias. J Chem Neuroanat 35:268–274CrossRefPubMedGoogle Scholar
  74. Weinberger DR, Gibson R, Coppola R, Jones DW, Molchan S, Sunderland T, Berman KF, Reba RC (1991) The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography. Arch Neurol 48:169–176CrossRefPubMedGoogle Scholar
  75. Wess J, Duttaroy A, Zhang W, Gomeza J, Cui Y, Miyakawa T, Bymaster FP, McKinzie L, Felder CC, Lamping KG, Faraci FM, Deng C, Yamada M (2003) M1–M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system. Receptors Channels 9:279–290CrossRefPubMedGoogle Scholar
  76. Wood PL, Etienne P, Lal S, Nair NP, Finlayson MH, Gauthier S, Palo J, Haltia M, Paetau A, Bird ED (1983) A post-mortem comparison of the cortical cholinergic system in Alzheimer’s disease and Pick’s disease. J Neurol Sci 62:211–217CrossRefPubMedGoogle Scholar
  77. Wyper DJ, Brown D, Patterson J, Owens J, Hunter R, Teasdale E, McCulloch J (1993) Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer’s disease. Eur J Nucl Med 20:379–386CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Molecular Psychiatry Laboratory, Division of Biological Psychiatry and Mental HealthFlorey Institute for Neuroscience and Mental HealthParkvilleAustralia
  2. 2.Victorian Brain Bank NetworkFlorey Institute for Neuroscience and Mental HealthParkvilleAustralia
  3. 3.Department of Anatomical PathologyAlfred HospitalMelbourneAustralia

Personalised recommendations