Skip to main content
SpringerLink
Log in

Prevention of Calbindin Recruitment into Nigral Dopamine Neurons from MPTP-Induced Degeneration in Macaca fascicularis

  • Conference paper
  • First Online:
The Basal Ganglia IX

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 58))

  • 979 Accesses

Abstract

Dopaminergic neurons in the substantia nigra pars compacta that express the calcium-binding protein calbindin selectively survive the cell death period in Parkinson’s disease. On the basis of this finding, we examined the preventive effect of calbindin recruitment into nigral dopamine neurons on toxic insults induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A recombinant adenoviral vector encoding the calbindin gene was injected unilaterally into the striatum of macaque monkeys. One to two weeks later, expression of calbindin through retrograde transduction was observed in cell bodies of nigral dopamine neurons on the side ipsilateral to vector treatment. In these monkeys, MPTP was administered systemically by repeated intravenous injections. Parkinsonian motor signs, such as akinesia, rigidity, and flexed posture, appeared less severely in the limbs contralateral to vector treatment. Histological analysis revealed that tyrosine hydroxylase immunoreactivity in the striatum was preserved better on the calbindin-recruited side, whereas α-synuclein was expressed in nigral dopamine neurons much more strongly on the nonrecruited side. These results indicate that gene delivery of calbindin into nigral dopamine neurons protects against MPTP-induced parkinsonian symptoms in monkeys.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

  • Björklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS and Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99: 2344–2349.

    Article  PubMed  Google Scholar 

  • Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick J, Tkatch T, Meredith GE and Surmeier DJ (2007) ‘Rejuvention’ protects neurons in mouse models of Parkinson’s disease. Nature 447: 1081–1086.

    Article  CAS  PubMed  Google Scholar 

  • Coyle JT and Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262: 689–695.

    Article  CAS  PubMed  Google Scholar 

  • Damier P, Hirsch EC, Agid Y and Graybiel AM (1999) The substantia nigra of the human brain. I. Nigrosomes and the nigral matrix, a compartmental organization based on calbindin D(28K) immunohistochemistry. Brain 122: 1421–1436.

    Article  PubMed  Google Scholar 

  • Dauer W and Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39: 889–909.

    Article  CAS  PubMed  Google Scholar 

  • During MJ, Samulski RJ, Elsworth JD, Kaplitt MG, Leone P, Xiao X, Li J, Freese A, Taylor JR, Roth RH, Sladek JR Jr, O’Malley KL and Redmond DE Jr. (1998) In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Ther 5: 820–827.

    Article  CAS  PubMed  Google Scholar 

  • During MJ, Kaplitt MG, Stern MB and Eidelberg D (2001) Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Hum Gene Ther 12: 1589–1591.

    CAS  PubMed  Google Scholar 

  • Fjord-Larsen L, Johansen JL, Kusk P, Tornoe J, Gronborg M, Rosenblad C and Wahlberg LU (2005) Efficient in vivo protection of nigral dopaminergic neurons by lentiviral gene transfer of a modified neurturin construct. Exp Neurol 195: 49–60.

    Article  CAS  PubMed  Google Scholar 

  • Gary DS, Sooy K, Chan SL, Christakos S and Mattson MP (2000) Concentration- and cell type-specific effects of calbindin D28k on vulnerability of hippocampal neurons to seizure-induced injury. Mol Brain Res 75: 89–95.

    Article  CAS  PubMed  Google Scholar 

  • Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ and Gerhardt GA (1996) Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380: 252–255.

    Article  CAS  PubMed  Google Scholar 

  • German DC, Manaye KF, Sonsalla PK and Brooks BA (1992) Midbrain dopaminergic cell loss in Parkinson’s disease and MPTP-induced parkinsonism: sparing of calbindin-D28k-containing cells. Ann NY Acad Sci 648: 42–62.

    Article  CAS  PubMed  Google Scholar 

  • Gibb WR (1992) Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson’s disease. Brain Res 581: 283–291.

    Article  CAS  PubMed  Google Scholar 

  • Ho BK, Alexianu ME, Colom LV, Mohamed AH, Serrano F and Appel SH (1996) Expression of calbindin-D28K in motoneuron hybrid cells after retroviral infection with calbindin-D28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity. Proc Natl Acad Sci USA 93: 6796–6801.

    Article  CAS  PubMed  Google Scholar 

  • Krieger C and Duchen MR (2002) Mitochondria, Ca21 and neurodegenerative disease. Eur J Pharmacol 447: 177–188.

    Article  CAS  PubMed  Google Scholar 

  • Lavoie B and Parent A (1991) Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. Neuroreport 2: 601–604.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Rychlik B, Chu C and Christakos S (1991) Evidence for calcium-reducing and excito-protective roles for the calcium-binding protein calbindin-D28k in cultured hippocampal neurons. Neuron 6: 41–51.

    Article  CAS  PubMed  Google Scholar 

  • McMahon A, Wong BS, Iacopino AM, Ng MC, Chi S and German DC (1998) Calbindin-D28k buffers intracellular calcium and promotes resistance to degeneration in PC12 cells. Mol Brain Res 54: 56–63.

    Article  CAS  PubMed  Google Scholar 

  • Mouatt-Prigent A, Agid Y and Hirsch EC (1994) Does the calcium binding protein calretinin protect dopaminergic neurons against degeneration in Parkinson’s disease? Brain Res 668: 62–70.

    Article  CAS  PubMed  Google Scholar 

  • Muramatsu S, Fujimoto K, Ikeguchi K, Shizuma N, Kawasaki K, Ono F, Shen Y, Wang L, Mizukami H, Kume A, Matsumura M, Nagatsu I, Urano F, Ichinose H, Nagatsu T, Terao K, Nakano I and Ozawa K (2002) Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther 13: 345–354.

    Article  CAS  PubMed  Google Scholar 

  • Murphy AN, Bredesen DE, Cortopassi G, Wang E and Fiskum G (1996) Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc Natl Acad Sci USA 93: 9893–9898.

    Article  CAS  PubMed  Google Scholar 

  • Orrenius S and Nicotera P (1994) The calcium ion and cell death. J Neural Transm Suppl 43: 1–11.

    CAS  PubMed  Google Scholar 

  • Orrenius S, Zhivotovsky B and Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4: 552–565.

    Article  CAS  PubMed  Google Scholar 

  • Parent A and Lavoie B (1993) The heterogeneity of the mesostriatal dopaminergic system as revealed in normal and parkinsonian monkeys. Adv Neurol 60: 25–24.

    CAS  PubMed  Google Scholar 

  • Piallat B, Benazzouz A and Benabid AL (1996) Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical studies. Eur J Neurosci 8: 1408–1414.

    Article  CAS  PubMed  Google Scholar 

  • Piallat B, Benazzouz A and Benabid AL (1999) Neuroprotective effect of chronic inactivation of the subthalamic nucleus in a rat model of Parkinson’s disease. J Neural Transm Suppl 55: 71–77.

    CAS  PubMed  Google Scholar 

  • Schwaller B, Meyer M and Schiffmann S (2002) ‘New’ functions for ‘old’ proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice. Cerebellum 1: 241–258.

    Article  CAS  PubMed  Google Scholar 

  • Smith RD, Zhang Z, Kurlan R, McDermott M and Gash DM (1993) Developing a stable bilateral model of parkinsonism in rhesus monkeys. Neuroscience 52: 7–16.

    Article  CAS  PubMed  Google Scholar 

  • Takada M, Matsumura M, Kojima J, Yamaji Y, Inase M, Tokuno H, Nambu A and Imai H (2000) Protection against dopaminergic nigrostriatal cell death by excitatory input ablation. Eur J Neurosci 12: 1771–1780.

    Article  CAS  PubMed  Google Scholar 

  • Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y and Hashimoto N (2005) Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 115: 102–109.

    CAS  PubMed  Google Scholar 

  • Verkhratsky A (2005) Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev 85: 201–279.

    Article  CAS  PubMed  Google Scholar 

  • Wilson CJ and Callaway JC (2000) Coupled oscillator model of the dopaminergic neuron of the substantia nigra. J Neurophysiol 83: 3084–3100.

    CAS  PubMed  Google Scholar 

  • Yamada T, McGeer PL, Baimbridge KG and McGeer EG (1990) Relative sparing in Parkinson’s disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res 526: 303–307.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. System Neuroscience Section, Primate Research Institute, Kyoto University Inuyama, Aichi, Tokyo, 484-8506, Japan

    Masahiko Takada, Ken-ichi Inoue, Shigehiro Miyachi, Haruo Okado & Atsushi Nambu

Authors
  1. Masahiko Takada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken-ichi Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigehiro Miyachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haruo Okado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Atsushi Nambu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahiko Takada .

Editor information

Editors and Affiliations

  1. Dept. Anatomy & Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, 1007 MB, Netherlands

    Hendrik Jan Groenewegen

  2. Medical Center, Vrije Universiteit, Van der Boechorststraat 7, Amsterdam, 1081 BT, Netherlands

    Pieter Voorn

  3. Department of Neurology, Vrije Universiteit Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV, Netherlands

    Henk W. Berendse

  4. Medical Center, Vrije Universiteit, Van der Boechorststraat 7, Amsterdam, 1081 BT, Netherlands

    Antonius B. Mulder

  5. Medical Centre, Radboud University Nijmegen, Geert Grooteplein 21a, Nijmegen, 6525 EZ, Netherlands

    Alexander R. Cools

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this paper

Cite this paper

Takada, M., Inoue, Ki., Miyachi, S., Okado, H., Nambu, A. (2009). Prevention of Calbindin Recruitment into Nigral Dopamine Neurons from MPTP-Induced Degeneration in Macaca fascicularis . In: Groenewegen, H., Voorn, P., Berendse, H., Mulder, A., Cools, A. (eds) The Basal Ganglia IX. Advances in Behavioral Biology, vol 58. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0340-2_29

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-0340-2_29

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-0339-6

  • Online ISBN: 978-1-4419-0340-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation