Skip to main content
SpringerLink
Log in

Synaptosomal Preparation and Its Application in Preclinical Studies

  • Protocol
  • First Online:
Translational Research Methods in Neurodevelopmental Disorders

Part of the book series: Neuromethods ((NM,volume 185))

Abstract

Here we reviewed both established and emerging approaches to study the synaptic function. After an overview on the synaptic morphology and function, we focused our attention on the use of synaptosomal preparation to investigate the presynaptic compartment, both in animal and human models with the final aim of better clarifying the synaptic dysfunction associated with neurological disorders. Additionally, we highlighted the recent application of synaptosomes for proteomic experiments as a valuable tool to examine the altered presynaptic machinery involved in neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis. We finally discussed the ways in which different synaptosomal preparations are revolutionizing our ability to investigate the complex mechanisms underlying the synaptic network.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Brodal A (1981) Neurological anatomy in relation to clinical medicine, 3rd edn. Oxford University Press, New York. 1053 pages, $35.00. Ann Neurol 10(6):584–584, 1981

    Google Scholar 

  2. Cajal, Santiago Ramón. Estructura del cerebelo

    Google Scholar 

  3. Fodstad H (2001) The neuron theory. Stereotact Funct Neurosurg 77(1–4):20–24

    Article  CAS  PubMed  Google Scholar 

  4. Sell GL, Barrow SL, McAllister AK (2020) Molecular composition of developing glutamatergic synapses. In: Synapse development and maturation [Internet]. Elsevier, pp 3–32. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128236727000016

    Chapter  Google Scholar 

  5. Burns ME, Augustine GJ (1995) Synaptic structure and function: dynamic organization yields architectural precision. Cell 83(2):187–194

    Article  CAS  PubMed  Google Scholar 

  6. Phillips GR, Huang JK, Wang Y, Tanaka H, Shapiro L, Zhang W et al (2001) The presynaptic particle web. Neuron 32(1):63–77

    Article  CAS  PubMed  Google Scholar 

  7. Hirokawa N, Sobue K, Kanda K, Harada A, Yorifuji H (1989) The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1. J Cell Biol 108(1):111–126

    Article  CAS  PubMed  Google Scholar 

  8. Landis DMD, Hall AK, Weinstein LA, Reese TS (1988) The organization of cytoplasm at the presynaptic active zone of a central nervous system synapse. Neuron 1(3):201–209

    Article  CAS  PubMed  Google Scholar 

  9. Dresbach T, Qualmann B, Kessels MM, Garner CC, Gundelfinger ED (2001) The presynaptic cytomatrix of brain synapses. Cell Mol Life Sci 58(1):94–116

    Article  CAS  PubMed  Google Scholar 

  10. Schoch S, Gundelfinger ED (2006) Molecular organization of the presynaptic active zone. Cell Tissue Res 326(2):379–391

    Article  CAS  PubMed  Google Scholar 

  11. Ziv NE, Garner CC (2004) Cellular and molecular mechanisms of presynaptic assembly. Nat Rev Neurosci 5(5):385–399

    Article  CAS  PubMed  Google Scholar 

  12. Michel K, Müller JA, Oprişoreanu A-M, Schoch S (2015) The presynaptic active zone: a dynamic scaffold that regulates synaptic efficacy. Exp Cell Res 335(2):157–164

    Article  CAS  PubMed  Google Scholar 

  13. Südhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27(1):509–547

    Article  PubMed  Google Scholar 

  14. Chua JJE, Kindler S, Boyken J, Jahn R (2010) The architecture of an excitatory synapse. J Cell Sci 123(6):819–823

    Article  CAS  PubMed  Google Scholar 

  15. Takamori S (2006) VGLUTs: ‘exciting’ times for glutamatergic research? Neurosci Res 55(4):343–351

    Article  CAS  PubMed  Google Scholar 

  16. Altrock WD, tom Dieck S, Sokolov M, Meyer AC, Sigler A, Brakebusch C et al (2003) Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon. Neuron 37(5):787–800

    Article  CAS  PubMed  Google Scholar 

  17. Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K et al (2002) Cast. J Cell Biol 158(3):577–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Takao-Rikitsu E, Mochida S, Inoue E, Deguchi-Tawarada M, Inoue M, Ohtsuka T et al (2004) Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release. J Cell Biol 164(2):301–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Doussau F (2000) The actin cytoskeleton and neurotransmitter release: an overview. Biochimie 82(4):353–363

    Article  CAS  PubMed  Google Scholar 

  20. Dehmelt L, Halpain S (2004) Actin and microtubules in neurite initiation: are MAPs the missing link? J Neurobiol 58(1):18–33

    Article  CAS  PubMed  Google Scholar 

  21. Boeckers TM (2006) The postsynaptic density. Cell Tissue Res 326(2):409–422

    Article  CAS  PubMed  Google Scholar 

  22. Sheng M, Hoogenraad CC (2007) The postsynaptic architecture of excitatory synapses: A more quantitative view. Annu Rev Biochem 76(1):823–847

    Article  CAS  PubMed  Google Scholar 

  23. Tao C-L, Liu Y-T, Sun R, Zhang B, Qi L, Shivakoti S et al (2018) Differentiation and characterization of excitatory and inhibitory synapses by cryo-electron tomography and correlative microscopy. J Neurosci 38(6):1493–1510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nakata K, Nagai T, Aruga J, Mikoshiba K (1998) Xenopus Zic family and its role in neural and neural crest development1During submission of this paper, Mizuseki et al., reported the Xenopus Zic-related-1 gene which was highly homologous to mouse Zic1 gene (Mizuseki et al., 1998). Accession no. Zic1, AB009564; Zic2, AB009565.1. Mech Dev 75(1–2):43–51

    Article  CAS  PubMed  Google Scholar 

  25. Rao A, Kim E, Sheng M, Craig AM (1998) Heterogeneity in the molecular composition of excitatory postsynaptic sites during development of hippocampal neurons in culture. J Neurosci 18(4):1217–1229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hebb CO, Whittaker VP (1958) Intracellular distributions of acetylcholine and choline acetylase. J Physiol 142(1):187–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. De Robertis E, De Iraldi AP, Rodriguez G, Gomez CJ (1961) On the isolation of nerve endings and synaptic vesicles. J Biophys Biochem Cytol 9(1):229–235

    Article  PubMed Central  Google Scholar 

  28. Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–88

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Whittaker VP (1969) The synaptosome. Struct Neurochem:327–364

    Google Scholar 

  30. Whittaker VP (1993) Thirty years of synaptosome research. J Neurocytol 22(9):735–742

    Article  CAS  PubMed  Google Scholar 

  31. Whittaker VP (1959) The isolation and characterization of acetylcholine-containing particles from brain. Biochem J 72(4):694–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Whittaker VP (1959) The identity of natural and synthetic ββ-dimethylacrylylcholine. Biochem J 71(1):32–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Whittaker VP (1968) The storage of transmitters in the central nervous system. Biochem J 109(3):20P–21P

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Whittaker VP (1968) The morphology of fractions of rat forebrain synaptosomes separated on continuous sucrose density gradients. Biochem J 106(2):412–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Whittaker VP (1968) Synaptic transmission. Proc Natl Acad Sci 60(4):1081–1091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cotman CW, Matthews DA (1971) Synaptic plasma membranes from rat brain synaptosomes: isolation and partial characterization. Biochim Biophys Acta BBA Biomembr 249(2):380–394

    Article  CAS  Google Scholar 

  37. Jones DG, Revell E (1970) The postnatal development of the synapse: A morphological approach utilizing synaptosomes: I. General features. Zeitschrift für Zellforschung und Mikroskopische Anatomie 111(2):179–194

    Article  CAS  PubMed  Google Scholar 

  38. Rizo J (2018) Mechanism of neurotransmitter release coming into focus: mechanism of neurotransmitter release. Protein Sci 27(8):1364–1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kringelbach ML, Cruzat J, Cabral J, Knudsen GM, Carhart-Harris R, Whybrow PC et al (2020) Dynamic coupling of whole-brain neuronal and neurotransmitter systems. Proc Natl Acad Sci 117(17):9566–9576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wilhelm BG, Mandad S, Truckenbrodt S, Krohnert K, Schafer C, Rammner B et al (2014) Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344(6187):1023–1028

    Article  CAS  PubMed  Google Scholar 

  41. Rosenberg T, Gal-Ben-Ari S, Dieterich DC, Kreutz MR, Ziv NE, Gundelfinger ED et al (2014) The roles of protein expression in synaptic plasticity and memory consolidation. Front Mol Neurosci 7:86

    Article  PubMed  PubMed Central  Google Scholar 

  42. Feligioni M, Raiteri L, Pattarini R, Grilli M, Bruzzone S, Cavazzani P et al (2003) The human immunodeficiency virus-1 protein Tat and its discrete fragments evoke selective release of acetylcholine from human and rat cerebrocortical terminals through species-specific mechanisms. J Neurosci 23(17):6810–6818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Biggi S, Buccarello L, Sclip A, Lippiello P, Tonna N, Rumio C et al (2017) Evidence of presynaptic localization and function of the c-Jun N-terminal kinase. Neural Plast 2017:1–14

    Article  Google Scholar 

  44. Hahn C-G, Banerjee A, MacDonald ML, Cho D-S, Kamins J, Nie Z et al (2009) The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses. Fox D, editor. PLoS One 4(4):e5251

    Article  PubMed  PubMed Central  Google Scholar 

  45. Witzmann FA, Arnold RJ, Bai F, Hrncirova P, Kimpel MW, Mechref YS et al (2005) A proteomic survey of rat cerebral cortical synaptosomes. Proteomics 5(8):2177–2201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tandon A, Bannykh S, Kowalchyk JA, Banerjee A, Martin TF, Balch WE (1998) Differential regulation of exocytosis by calcium and CAPS in semi-intact Synaptosomes. Neuron 21(1):147–154

    Article  CAS  PubMed  Google Scholar 

  47. Bajor M, Michaluk P, Gulyassy P, Kekesi AK, Juhasz G, Kaczmarek L (2012) Synaptic cell adhesion molecule-2 and collapsin response mediator protein-2 are novel members of the matrix metalloproteinase-9 degradome: proteomic discovery of MMP-9 substrates. J Neurochem 122(4):775–788

    Article  CAS  PubMed  Google Scholar 

  48. Dunkley PR, Jarvie PE, Robinson PJ (2008) A rapid Percoll gradient procedure for preparation of synaptosomes. Nat Protoc 3(11):1718–1728

    Article  CAS  PubMed  Google Scholar 

  49. Fedder K, Sabo S (2015) On the role of glutamate in presynaptic development: possible contributions of presynaptic NMDA receptors. Biomol Ther 5(4):3448–3466

    CAS  Google Scholar 

  50. Marcelli S, Ficulle E, Iannuzzi F, Kövari E, Nisticò R, Feligioni M (2017) Targeting SUMO-1ylation contrasts synaptic dysfunction in a mouse model of Alzheimer’s disease. Mol Neurobiol 54(8):6609–6623

    Article  CAS  PubMed  Google Scholar 

  51. Biesemann C, Grønborg M, Luquet E, Wichert SP, Bernard V, Bungers SR et al (2014) Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting. EMBO J 33(2):157–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Marcelli S, Iannuzzi F, Ficulle E, Mango D, Pieraccini S, Pellegrino S et al (2019) The selective disruption of presynaptic JNK2/STX1a interaction reduces NMDA receptor-dependent glutamate release. Sci Rep 9(1):7146

    Article  PubMed  PubMed Central  Google Scholar 

  53. Nisticò R, Florenzano F, Mango D, Ferraina C, Grilli M, Di Prisco S et al (2015) Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release. Sci Rep 5:9035

    Article  PubMed  PubMed Central  Google Scholar 

  54. Grilli M, Summa M, Salamone A, Olivero G, Zappettini S, Di Prisco S et al (2012) In vitro exposure to nicotine induces endocytosis of presynaptic AMPA receptors modulating dopamine release in rat nucleus accumbens nerve terminals. Neuropharmacology 63(5):916–926

    Article  CAS  PubMed  Google Scholar 

  55. Pittaluga A, Segantini D, Feligioni M, Raiteri M (2005) Extracellular protons differentially potentiate the responses of native AMPA receptor subtypes regulating neurotransmitter release. Br J Pharmacol 144(2):293–299

    Article  CAS  PubMed  Google Scholar 

  56. Tuz K, Peña-Segura C, Franco R, Pasantes-Morales H (2004) Depolarization, exocytosis and amino acid release evoked by hyposmolarity from cortical synaptosomes. Eur J Neurosci 19(4):916–924

    Article  PubMed  Google Scholar 

  57. Lin TY, Lu CW, Huang SK, Wang SJ (2012) Curcumin inhibits glutamate release from rat prefrontal nerve endings by affecting vesicle mobilization. Int J Mol Sci 13(7):9097–9109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Langer SZ (2008) Presynaptic autoreceptors regulating transmitter release. Neurochem Int 52(1–2):26–30

    Article  CAS  PubMed  Google Scholar 

  59. Pittaluga A, Raiteri L, Longordo F, Luccini E, Barbiero VS, Racagni G et al (2007) Antidepressant treatments and function of glutamate ionotropic receptors mediating amine release in hippocampus. Neuropharmacology 53(1):27–36

    Article  CAS  PubMed  Google Scholar 

  60. Langer SZ (2008) Therapeutic use of release-modifying drugs. In: Südhof TC, Starke K (eds) Pharmacology of neurotransmitter release [Internet]. Springer, Berlin/Heidelberg, pp 561–573. Available from: http://link.springer.com/10.1007/978-3-540-74805-2_17

    Chapter  Google Scholar 

  61. Vergassola M, Olivero G, Cisani F, Usai C, Bossi S, Puliti A et al (2018) Presynaptic mGlu1 receptors control GABAB receptors in an antagonist-like manner in mouse cortical GABAergic and glutamatergic nerve endings. Front Mol Neurosci [Internet] 11. Available from: https://www.frontiersin.org/article/10.3389/fnmol.2018.00324/full

  62. Giribaldi F, Milanese M, Bonifacino T, Anna Rossi PI, Di Prisco S, Pittaluga A et al (2013) Group I metabotropic glutamate autoreceptors induce abnormal glutamate exocytosis in a mouse model of amyotrophic lateral sclerosis. Neuropharmacology 66:253–263

    Article  CAS  PubMed  Google Scholar 

  63. Picone P, Porcelli G, Bavisotto CC, Nuzzo D, Galizzi G, Biagio PLS et al (2021) Synaptosomes: new vesicles for neuronal mitochondrial transplantation. J Nanobiotechnol 19(1):1–15

    Article  Google Scholar 

  64. Gulyássy P, Puska G, Györffy BA, Todorov-Völgyi K, Juhász G, Drahos L et al (2020) Proteomic comparison of different synaptosome preparation procedures. Amino Acids 52(11–12):1529–1543

    Article  PubMed  PubMed Central  Google Scholar 

  65. Levi G, Raiteri M (1973) Detectability of high and low affinity uptake systems for GABA and glutamate in rat brain slices and synaptosomes. Life Sci 12(2):81–88

    Article  CAS  Google Scholar 

  66. Nuzzo T, Feligioni M, Cristino L, Pagano I, Marcelli S, Iannuzzi F et al (2019) Free d-aspartate triggers NMDA receptor-dependent cell death in primary cortical neurons and perturbs JNK activation, Tau phosphorylation, and protein SUMOylation in the cerebral cortex of mice lacking d-aspartate oxidase activity. Exp Neurol 317:51–65

    Article  CAS  PubMed  Google Scholar 

  67. Serval V, Barbeito L, Pittaluga A, Cheramy A, Lavielle S, Glowinski J (1990) Competitive inhibition of N-acetylated-alpha-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-beta-linked L-glutamate. J Neurochem 55(1):39–46

    Article  CAS  PubMed  Google Scholar 

  68. Nicholls DG, Sihra TS, Sanchez-Prieto J (1987) Calcium-dependent and-independent release of glutamate from synaptosomes monitored by continuous fluorometry. J Neurochem 49(1):50–57

    Article  CAS  PubMed  Google Scholar 

  69. Marks B, McMahon HT (1998) Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals. Curr Biol 8(13):740–749

    Article  CAS  PubMed  Google Scholar 

  70. Herrero I, Miras-Portugal MT, Sánchez-Prieto J (1994) Rapid desensitization of the metabotropic glutamate receptor that facilitates glutamate release in rat cerebrocortical nerve terminals. Eur J Neurosci 6(1):115–120

    Article  CAS  PubMed  Google Scholar 

  71. Rodríguez-Moreno A, Sistiaga A, Lerma J, Sánchez-Prieto J (1998) Switch from facilitation to inhibition of excitatory synaptic transmission by Group I mGluR desensitization. Neuron 21(6):1477–1486

    Article  PubMed  Google Scholar 

  72. Lonart G, Simsek-Duran F (2006) Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation. Brain Res 1107(1):42–51

    Article  CAS  PubMed  Google Scholar 

  73. Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock WP et al (2005) Proteomic analysis of in vivo phosphorylated synaptic proteins. J Biol Chem 280(7):5972–5982

    Article  CAS  PubMed  Google Scholar 

  74. Schrimpf SP, Meskenaite V, Brunner E, Rutishauser D, Walther P, Eng J et al (2005) Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass spectrometry. Proteomics 5(10):2531–2541

    Article  CAS  PubMed  Google Scholar 

  75. Munton RP, Tweedie-Cullen R, Livingstone-Zatchej M, Weinandy F, Waidelich M, Longo D et al (2007) Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse Synaptosomal preparations. Mol Cell Proteomics 6(2):283–293

    Article  CAS  PubMed  Google Scholar 

  76. Pronot M, Kieffer F, Gay A-S, Debayle D, Forquet R, Poupon G et al (2021) Proteomic identification of an endogenous synaptic SUMOylome in the developing rat brain [Internet]. Available from: www.frontiersin.org/articles/10.3389/fnmol.2021.780535/abstract

  77. Hardy J, Cowburn R, Barton A, Reynolds G, Lofdahl E, O’Carroll A-M et al (1987) Region-specific loss of glutamate innervation in Alzheimer’s disease. Neurosci Lett 73(1):77–80

    Article  CAS  PubMed  Google Scholar 

  78. Nordberg A, Winblad B (1986) Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains. Neurosci Lett 72(1):115–120

    Article  CAS  PubMed  Google Scholar 

  79. Hardy J, Adolfsson R, Alafuzoff I, Bucht G, Marcusson J, Nyberg P et al (1985) Transmitter deficits in Alzheimer’s disease. Neurochem Int 7(4):545–563

    Article  CAS  PubMed  Google Scholar 

  80. Wang J-Z, Liu F (2008) Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol 85(2):148–175

    Article  CAS  PubMed  Google Scholar 

  81. Wood J (1996) Partial characterisation of murine huntingtin and apparent variations in the subcellular localisation of huntingtin in human, mouse and rat brain. Hum Mol Genet 5(4):481–487

    Article  CAS  PubMed  Google Scholar 

  82. Postupna NO, Latimer CS, Dirk Keene C, Montine KS, Montine TJ, Darvas M (2018) Flow cytometric evaluation of crude synaptosome preparation as a way to study synaptic alteration in neurodegenerative diseases. In: Murphy KM (ed) Synaptosomes [Internet]. Springer, New York, pp 297–310. Available from: http://link.springer.com/10.1007/978-1-4939-8739-9_17

    Chapter  Google Scholar 

  83. Pifl C, Rajput A, Reither H, Blesa J, Cavada C, Obeso JA et al (2014) Is Parkinson’s disease a vesicular dopamine storage disorder? Evidence from a study in isolated synaptic vesicles of human and nonhuman primate striatum. J Neurosci 34(24):8210–8218

    Article  PubMed  PubMed Central  Google Scholar 

  84. Haberland N, Hetey L (1987) Studies in postmortem dopamine uptake: II. Alterations of the synaptosomal catecholamine uptake in postmortem brain regions in schizophrenia. J Neural Transm 68(3–4):303–313

    Article  CAS  PubMed  Google Scholar 

  85. Scarr E, Gray L, Keriakous D, Robinson P, Dean B (2006) Increased levels of SNAP-25 and synaptophysin in the dorsolateral prefrontal cortex in bipolar I disorder. Bipolar Disord 8(2):133–143

    Article  CAS  PubMed  Google Scholar 

  86. Goldstein I, Levy T, Galili D, Ovadia H, Yirmiya R, Rosen H et al (2006) Involvement of Na+, K+-ATPase and endogenous digitalis-like compounds in depressive disorders. Biol Psychiatry 60(5):491–499

    Article  CAS  PubMed  Google Scholar 

  87. Grant SGN (2006) The synapse proteome and phosphoproteome: a new paradigm for synapse biology. Biochem Soc Trans 34(1):59–63

    Article  CAS  PubMed  Google Scholar 

  88. Bai F, Witzmann FA (2007) Synaptosome proteomics. In: Bertrand E, Faupel M (eds) Subcellular proteomics [Internet]. Springer, Dordrecht, pp 77–98. Available from: http://link.springer.com/10.1007/978-1-4020-5943-8_6

    Chapter  Google Scholar 

  89. Salvaterra PM, Matthews DA (1980) Isolation of rat brain subcellular fraction enriched in putative neurotransmitter receptors and synaptic junctions. Neurochem Res 5(2):181–195

    Article  CAS  PubMed  Google Scholar 

  90. Tsetsenis T, Boucard AA, Arac D, Brunger AT, Sudhof TC (2014) Direct visualization of trans-synaptic neurexin-neuroligin interactions during synapse formation. J Neurosci 34(45):15083–15096

    Article  PubMed  PubMed Central  Google Scholar 

  91. Kornau H, Schenker L, Kennedy M, Seeburg P (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269(5231):1737–1740

    Article  CAS  PubMed  Google Scholar 

  92. Naisbitt S, Kim E, Tu JC, Xiao B, Sala C, Valtschanoff J et al (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23(3):569–582

    Article  CAS  PubMed  Google Scholar 

  93. Ehrlich I (2004) Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci 24(4):916–927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Srivastava S, Osten P, Vilim FS, Khatri L, States B Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 21:581–591

    Google Scholar 

  95. Kennedy MB (2000) Signal-processing machines at the postsynaptic density. Science 290(5492):750–754

    Article  CAS  PubMed  Google Scholar 

  96. Murphy KM (2018) Introduction to synaptosomes. Neuromethods 141:3–6

    Article  CAS  Google Scholar 

  97. Plum S, Eggers B, Helling S, Stepath M, Theiss C, Leite REP et al (2020) Proteomic characterization of synaptosomes from human substantia Nigra indicates altered mitochondrial translation in Parkinson’s disease. Cell 9(12)

    Google Scholar 

  98. Ahmad F, Liu P (2020) Synaptosome as a tool in Alzheimer’s disease research. Brain Res 1746

    Google Scholar 

  99. Jhou J-F, Tai H-C (2017) The study of postmortem human synaptosomes for understanding Alzheimer’s disease and other neurological disorders: a review. Neurol Ther 6(Suppl 1):57–68

    Article  PubMed  PubMed Central  Google Scholar 

  100. Sokolow S, Henkins KM, Bilousova T, Gonzalez B, Vinters HV, Miller CA et al (2015) Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer’s disease. J Neurochem 133(3):368–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC et al (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48(6):913–922

    Article  CAS  PubMed  Google Scholar 

  102. Tai H-C, Wang BY, Serrano-Pozo A, Frosch MP, Spires-Jones TL, Hyman BT (2014) Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease. Acta Neuropathol Commun 2(1)

    Google Scholar 

  103. Tai H-C, Serrano-Pozo A, Hashimoto T, Frosch MP, Spires-Jones TL, Hyman BT (2012) The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol 181(4):1426–1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Fein JA, Sokolow S, Miller CA, Vinters HV, Yang F, Cole GM et al (2008) Co-localization of amyloid beta and tau pathology in Alzheimer’s disease synaptosomes. Am J Pathol 172(6):1683–1692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27(5):457–464

    Article  CAS  PubMed  Google Scholar 

  106. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572–580

    Article  CAS  PubMed  Google Scholar 

  107. Fonseca-Ornelas L, Viennet T, Rovere M, Ericsson M, Arthanari H, Correspondence DJS et al (2021) Altered conformation of α-synuclein drives dysfunction of synaptic vesicles in a synaptosomal model of Parkinson’s disease. Cell Rep 36

    Google Scholar 

  108. Betzer C, Movius AJ, Shi M, Gai W-P, Zhang J, Jensen PH (2015) Identification of synaptosomal proteins binding to monomeric and oligomeric α-synuclein. PLoS One 10(2):e0116473

    Article  PubMed  PubMed Central  Google Scholar 

  109. Sapp E, Seeley C, Iuliano M, Weisman E, Vodicka P, DiFiglia M et al (2020) Protein changes in synaptosomes of Huntington’s disease knock-in mice are dependent on age and brain region. Neurobiol Dis 141:104950

    Article  CAS  PubMed  Google Scholar 

  110. Ross SM, Roy DN, Spencer PS (1985) ?-N-Oxalylamino-l-alanine: action on high-affinity transport of neurotransmitters in rat brain and spinal cord synaptosomes. J Neurochem 44(3):886–892

    Article  CAS  PubMed  Google Scholar 

  111. Atterwill CK, Neal MJ (1976) The subcellular distribution of [14C] GABA and [3H] dopamine in the retina. J Neurochem 27(2):529–537

    Article  CAS  PubMed  Google Scholar 

  112. Giacobini E, Hökfelt T, Kerpel-Fronius S, Koslow SH, Mitchard M, Noré B (1971) Micro-scale procedure for the preparation of subcellular fractions from individual autonomic ganglia. J Neurochem 18(2):223–231

    Article  CAS  PubMed  Google Scholar 

  113. Wilson WS, Cooper JR (1972) The preparation of cholinergic synaptosomes from bovine superior cervical ganglia. J Neurochem 19(12):2779–2790

    Article  CAS  PubMed  Google Scholar 

  114. Jonakait GM, Markey KA, Goldstein M, Dreyfus CF, Black IB (1985) Selective expression of high-affinity uptake of catecholamines by transiently catecholaminergic cells of the rat embryo: studies in vivo and in vitro. Dev Biol 108(1):6–17

    Article  CAS  PubMed  Google Scholar 

  115. Dowdall MJ, Zimmermann H (1977) The isolation of pure cholinergic nerve terminal sacs (T-sacs) from the electric organ of juvenile Torpedo. Neuroscience 2(3):405–421

    Article  CAS  PubMed  Google Scholar 

  116. Michaelson DM, Sokolovsky M (1978) Induced acetylcholine release from active purely cholinergic Torpedo synaptosomes. J Neurochem 30(1):217–230

    Article  CAS  PubMed  Google Scholar 

  117. Morel N, Israël M, Manaranche R, Lesbats B (1979) Stimulation of cholinergic synaptosomes isolated fkom torpedo electric organ. In: Progress in brain research [Internet]. Elsevier, pp 191–202. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0079612308646336

    Google Scholar 

  118. Santiapillai NF, Gray SR, Phillips RE, Richardson PJ (1989) Isolation of nerve terminals from crustacean muscle. J Neurochem 53(5):1527–1535

    Article  CAS  PubMed  Google Scholar 

  119. Mehta PP, Battenberg E, Wilson MC (1996) SNAP-25 and synaptotagmin involvement in the final Ca(2+)-dependent triggering of neurotransmitter exocytosis. Proc Natl Acad Sci 93(19):10471–10476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Michaelis ML, Jiang L, Michaelis EK (2017) Isolation of synaptosomes, synaptic plasma membranes, and synaptic junctional complexes. In: Poulopoulos A (ed) Synapse development [Internet]. Springer, New York, pp 107–119. Available from: http://link.springer.com/10.1007/978-1-49396688-2_9-

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Neuronal Cell Signaling, European Brain Research Institute (EBRI) Rita Levi Montalcini Foundation, Rome, Italy

    Marco Feligioni & Lucia Buccarello

  2. Department of Neurorehabilitation Sciences, Casa di Cura del Policlinico, Milan, Italy

    Marco Feligioni & Massimo Corbo

  3. Need Institute, Milan, Italy

    Lucia Buccarello

  4. Fondazione Pisana per la Scienza, Pisa, Italy

    Kambiz Hassanzadeh

Authors
  1. Marco Feligioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucia Buccarello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kambiz Hassanzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo Corbo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Feligioni .

Editor information

Editors and Affiliations

  1. CNRS UMR7275, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

    Stéphane Martin

  2. UMR1253, iBrain, University of Tours, Inserm, Tours, France

    Frédéric Laumonnier

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Feligioni, M., Buccarello, L., Hassanzadeh, K., Corbo, M. (2022). Synaptosomal Preparation and Its Application in Preclinical Studies. In: Martin, S., Laumonnier, F. (eds) Translational Research Methods in Neurodevelopmental Disorders. Neuromethods, vol 185. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2569-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2569-9_2

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2568-2

  • Online ISBN: 978-1-0716-2569-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation