Download PDF
Nuklearmedizin 2011; 50(04): 155-156
DOI: 10.3413/Nukmed-0371-10-12
Review
Schattauer GmbH

In vivo imaging neurotransmitter function

The rat 6-hydroxydopamine model and its relevance for human Parkinson’s diseaseIn-vivo-Bildgebung der NeurotransmitterfunktionDas Ratten-6-Hydroxydopamin-Modell in seiner Bedeutung für die Parkinson-Erkrankung des Menschen
S. Nikolaus
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
R. Larisch
2   Clinic of Nuclear Medicine, Clinic of Lüdenscheid, Germany
,
H. Vosberg
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
M. Beu
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
H. Hautzel
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
A. Wirrwar
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
H.-W. Mueller
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
,
C. Antke
1   Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

received: 06 December 2010

accepted in revised form: 14 February 2011

Publication Date:
28 December 2017 (online)

    Permissions and Reprints

Summary

This article gives an overview of those small animal imaging studies which have been conducted on neurotransmitter function in the rat 6-hydoxydopamine (6-OHDA) model of Parkinson’s disease, and discusses findings with respect to the outcome of clinical studies on Parkinsonian patients.

Zusammenfassung

Diese Arbeit gibt eine Übersicht über die bildgebenden Untersuchungen zur Neurotransmitterfunktion, die am 6-Hydroxydopamin- Modell der Ratte durchgeführt wurden. Die Befunde werden im Hinblick auf die Ergebnisse klinischer Studien an Patienten mit Morbus Parkinson diskutiert.

Keywords

Parkinson's disease - PET - SPECT - dopamine - 6-hydroxydopamine model - small animal imaging

Schlüsselwörter

Morbus Parkinson - PET - SPECT - Dopamin - 6-Hydroxydopamin-Modell - Kleintierbildgebung
 

  • References

  • 1 Björklund LM, Sanchez-Pernaute R, Chung S. et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 2002; 99: 2344-2349.
    CrossrefPubMedGoogle Scholar
  • 2 Bohnen NI, Albin RL, Koeppe RA. et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cereb Blood Flow Metab 2006; 26: 1198-1212.
    CrossrefPubMedGoogle Scholar
  • 3 Booij J, de Bruin K, Habraken JB. et al. Imaging of dopamine transporters in rats using high-resolution pinhole single-photon emission tomography. Eur J Nucl Med Mol Imaging 2002; 29: 1221-1224.
    CrossrefPubMedGoogle Scholar
  • 4 Brotchie JM. CB1 cannabinoid receptor signalling in Parkinson's disease. Curr Opin Pharmacol 2003; 3: 54-61.
    CrossrefPubMedGoogle Scholar
  • 5 Brownell AL, Livni E, Galpern W, Isacson W. In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants. Ann Neurol 1998; 43: 387-390.
    CrossrefPubMedGoogle Scholar
  • 6 Casteels C, Vermaelen P, Nuyts J. et al. Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med 2006; 47: 1858-1866.
    PubMedGoogle Scholar
  • 7 Casteels C, Lauwers E, Baitar A. et al. In vivo type 1 cannabinoid receptor mapping in the 6-hydroxydopamine lesion rat model of Parkinson's disease. Brain Res 2010; 1316: 153-262.
    CrossrefPubMedGoogle Scholar
  • 8 Caudle WM, Zhang J. Glutamate, excitotoxicity, and programmed cell death in Parkinson disease. Exp Neurol 2009; 220 (02) 30-33.
    Google Scholar
  • 9 Chen YCI, Galpern WR, Brownell AL. et al. Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, microdialysis, and behavioral data. Magn Reson Med 1997; 38: 389-398.
    CrossrefPubMedGoogle Scholar
  • 10 Chen YI, Brownell AL, Galpern W. et al. Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment. Neuroreport 1999; 10: 2881-2886.
    CrossrefPubMedGoogle Scholar
  • 11 Cicchetti F, Brownell AL, Williams K. et al. Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 2002; 15: 991-998.
    CrossrefPubMedGoogle Scholar
  • 12 Collantes M, Penuelas I, Alvarez-Erviti L. et al. Use of 11C-(+)-alpha -dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease. Rev Esp Med Nucl 2008; 27: 103-111.
    CrossrefPubMedGoogle Scholar
  • 13 Cumming P, Ase A, Diksic M. et al. Metabolism and blood-clearanceof L-3,4-dihydroxy-[3H]phenylalanine [3H]DOPAand 6-{18F]fluoro-L-DOPA in the rat. Biochem Pharmacol 1995; 50: 943-946.
    CrossrefPubMedGoogle Scholar
  • 14 Duty S. Therapeutic potential of targeting group III metabotropic glutamate receptors in the treatment of Parkinson's disease. Br J Pharmacol 2010; 161: 271-287.
    CrossrefPubMedGoogle Scholar
  • 15 Ferré S, Fuxe K. Dopamine denervation leads to an increase in the intramembrane interactions between adenosine A2 and dopamine D2 receptors in the neostriatum. Brain Res 1992; 595: 124-130.
    Google Scholar
  • 16 Fox SH, Chuang R, Brotchie JM. Serotonin and Parkinson's disease: On movement, mood, and madness. Mov Disord 2009; 24: 1255-1266.
    CrossrefPubMedGoogle Scholar
  • 17 Honer M, Hengerer B, Blagoev M. et al. Comparison of [18F]FDOPA, [18F]FMT and [18F]FECNT for imaging dopaminergic neurotransmission in mice. Nucl Med Biol 2006; 33: 607-614.
    CrossrefPubMedGoogle Scholar
  • 18 Hume SP, Opacka-Juffry J, Myers R. et al. Effect of L-dopa and 6-hydroxydopamine lesioning on [11C]raclopride binding in rat striatum quantified using PET. Synapse 1995; 21: 45-53.
    CrossrefPubMedGoogle Scholar
  • 19 Hume SP, Lammertsma AA, Myers R. et al. The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. J Neurosci Meth 1996; 67: 103-112.
    PubMedGoogle Scholar
  • 20 Inaji M, Okauchi T, Ando K. et al. Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats. Brain Res 2005; 1064: 136-145.
    CrossrefPubMedGoogle Scholar
  • 21 Inaji M, Yoshizaki T, Okauchi T. et al. In vivo PET measurements with [11C]PE2I to evaluate fetal mesencephalic transplantations to unilateral 6-OHDA-lesioned rats. Cell Transplant 2005; 14: 655-663.
    CrossrefPubMedGoogle Scholar
  • 22 Jackson J, Chapon C, Jones W. et al. In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson's disease. J Neurosci Methods 2009; 183: 141-148.
    CrossrefPubMedGoogle Scholar
  • 23 Jordan S, Eberling JL, Bankiewicz KS. et al. 6-[18F] fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates. Brain Res 1997; 750: 264-276.
    CrossrefPubMedGoogle Scholar
  • 24 Klein RL, Dayton RD, Terry TL. et al. PET imaging in rats to discern temporal onset differences between 6-hydroxydopamine and tau gene vector neurodegeneration models. Brain Res 2009; 1259: 113-122.
    CrossrefPubMedGoogle Scholar
  • 25 Kuhar MJ, Couceyro PR, Lambert PD. Catecholamines. Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Whler MD. Basic Neurochemistry - Molecular, Cellular and Medical Aspects.. Baltimore: Lippincott, Williams & Wilkins; 1998: 243-261.
    Google Scholar
  • 26 Nguyen TV, Brownell AL, Chen YCI. et al. Detection of the effects of dopamine receptor sensitivity using pharmacological MRI and correlations with PET. Synapse 2000; 36: 57-65.
    CrossrefPubMedGoogle Scholar
  • 27 Nikolaus S, Huston JP, Körber B. et al. Pretreatment with neurokinin substance P but not with cholecystokinin-8S can alleviate functional deficits of partial nigrostriatal 6-hydroxydopamine lesion. Peptides 1997; 18: 1161-1168.
    CrossrefPubMedGoogle Scholar
  • 28 Nikolaus S, Huston JP, Schwarting RKW. Pretreatment with fragments of substance-P or with cholecystokinin differentially affects revovery from subtotal nigrostriatal 6-hydroxydopamine lesion. Neural Plast 1999; 6: 77-89.
    CrossrefPubMedGoogle Scholar
  • 29 Nikolaus S, Larisch R, Beu M. et al. Imaging of striatal dopamine D2 receptors with a PET system for small laboratory animals in comparison with storage phosphor autoradiography: a validation study with [18F]N-methyl-benperidol. J Nucl Med 2001; 42: 1691-1661.
    PubMedGoogle Scholar
  • 30 Nikolaus S, Larisch R, Beu M. et al. Bilateral increase in striatal dopamine D2 receptor density in the 6-hydroxydopamine-lesioned rat: a serial in vivo investigation with small animal PET. Eur J Nucl Med Mol Imaging 2003; 30: 390-395.
    CrossrefPubMedGoogle Scholar
  • 31 Nikolaus S, Larisch R, Beu M. et al. In vivo measurement of D2 receptor density and affinity for 18F-(3-N-methyl)benperidol in the rat striatum with a PET system for small laboratory animals. J Nucl Med 2003; 44: 618-624.
    PubMedGoogle Scholar
  • 32 Nikolaus S, Beu M, Wirrwar A. et al. The contribution of small animal positron emission tomography to the neurosciences - a critical evaluation. Rev Neurosci 2004; 15: 131-156.
    Google Scholar
  • 33 Nikolaus S, Wirrwar A, Antke C. et al. Stand der Kleintierbildgebung mit hochauflösender SPECT. Nuklearmedizin 2005; 6: 257-266.
    Article in Thieme ConnectGoogle Scholar
  • 34 Nikolaus S, Antke C, Kley K. et al. Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans. Rev Neurosci 2007; 18: 439-472.
    Google Scholar
  • 35 Nikolaus S, Larisch R, Beu M. et al. Investigating the dopaminergic synapse in vivo. II. Molecular imaging studies in small laboratory animals. Rev Neurosci 2007; 18: 473-505.
    Google Scholar
  • 36 Nikolaus S, Antke C, Müller HW. In vivo imaging of synaptic function in the central nervous system. I. Movement disorders and dementia. Behav Brain Res 2009; 204: 1-31.
    CrossrefPubMedGoogle Scholar
  • 37 Nikolaus S, Antke C, Müller HW. In vivo imaging of synaptic function in the central nervous system. II. Mental and affective disorders. Behav Brain Res 2009; 204: 32-66.
    CrossrefPubMedGoogle Scholar
  • 38 Nikolaus S, Beu M, Antke C, Müller HW. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders - Results from in vivo imaging studies. Rev Neurosci 2010; 21: 119-139.
    Google Scholar
  • 39 Opacka-Juffry J, Ashworth S, Hume SP. et al. GDNF protects against 6-hydroxydopamine lesion: in vivo study with microdialysis and PET. Neuroreport 1995; 7: 348-352.
    PubMedGoogle Scholar
  • 40 Opacka-Juffry J, Ashworth S, Sullivan AM. et al. Lack of permanent nigrostriatal dopamine deficit following 6-hydroxydopamine injection into the rat striatum. J Neural Transm 1996; 103: 1429-1434.
    CrossrefPubMedGoogle Scholar
  • 41 Pellegrino D, Cicchetti F, Wang X. et al. Modulation of dopaminergic and glutamatergic brain function: PET studies on parkinsonian rats. J Nucl Med 2007; 48: 1147-1153.
    CrossrefPubMedGoogle Scholar
  • 42 Pritzel M, Huston JP, Sarter M. Behavioral and neuronal reorganization after unilateral substantia nigra lesions: evidence for increased interhemispheric nigrostriatal projections. Neuroscience 1983; 9: 879-888.
    CrossrefPubMedGoogle Scholar
  • 43 Santiago RM, Barbieiro J, Lima MMS. et al. Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson's disease are predominantly associated with serotonin and dopamine. Prog Neuropsychopharmacol Biol Psychiat 2010; 34: 1140-1114.
    Google Scholar
  • 44 Scherfler C, Donnemiller E, Schocke M. et al. Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT. Neuroimage 2002; 17: 128-141.
    CrossrefPubMedGoogle Scholar
  • 45 Schramm NU, Ebel G, Engeland U. et al. High-resolution SPECT using multipinhole collimation. IEEE Trans Nucl Sci 2003; 50: 315-320.
    CrossrefGoogle Scholar
  • 46 Schwarting RKW, Huston JP. The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol 1996; 50: 275-331.
    CrossrefPubMedGoogle Scholar
  • 47 Sossi V, Holden JE, Topping GJ. et al. In vivo measurement of density and affinity of the monoamine vesicular transporter in a unilateral 6-hydroxydopamine rat model of PD. J Cereb Blood Flow Metab 2007; 27: 1407-1415.
    CrossrefPubMedGoogle Scholar
  • 48 Sossi V, Dinelle K, Topping GJ. et al. Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's: an in vivo imaging study. J Neurochem 2009; 109: 85-92.
    CrossrefPubMedGoogle Scholar
  • 49 Sossi V, Dinelle K, Schulzer M. et al. Levodopa and pramipexole effects on presynaptic dopamine PET markers and estimated dopamine release. Eur J Nucl Med Mol Imaging 2010; 37: 2364-2370.
    CrossrefPubMedGoogle Scholar
  • 50 Strome EM, Cepeda IL, Sossi V, Doudet DJ. Evaluation of the integrity of the dopamine system in a rodent model of Parkinson's disease: small animal positron emission tomography compared to behavioral assessment and autoradiography. Mol Imaging Biol 2006; 8: 292-299.
    CrossrefPubMedGoogle Scholar
  • 51 Sullivan AM, Opacka-Juffry J, Blunt SB. Long-term protection of the rat nigrostriatal dopaminergic system by glial cell line-derived neurotrophic factor against 6-hydroxydopamine in vivo . Eur J Neurosci 1998; 10: 57-63.
    CrossrefPubMedGoogle Scholar
  • 52 Sun W, Sugiyama K, Fang X. et al. Different striatal D2-like receptor function in an early stage after unilateral striatal lesion and medial forebrain bundle lesion in rats. Brain Res 2010; 1317: 227-235.
    CrossrefPubMedGoogle Scholar
  • 53 Wang JL, Shunichi O, Parhi AK. et al. In vivo studies on SERT-selektive [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease. Nucl Med Biol 2010; 37: 479-486.
    CrossrefPubMedGoogle Scholar
  • 54 Wu C, van der Have F, Vastenhouw B. et al. Absolute quantitative total-body small-animal SPECT with focusing pinholes. Eur J Nucl Med Mol Imaging 2010; 37: 2127-2135.
    CrossrefPubMedGoogle Scholar
  • 55 Zhu A, Wang X, Yu M. et al. Evaluation of four pyridine analogs to characterize 6-OHDA-induced modulation of mGluR5 function in rat brain using microPET studies. J Cereb Blood Flow Metab 2007; 27: 1623-1631.
    CrossrefPubMedGoogle Scholar