Skip to main content
SpringerLink
Log in

Non-invasive MR Imaging of Neurodegeneration in a Rodent Model of Parkinson’s Disease

  • Protocol
  • First Online:
Book cover Magnetic Resonance Neuroimaging

Part of the book series: Methods in Molecular Biology ((MIMB,volume 711))

  • 5534 Accesses

Abstract

Neurotoxin-based rodent models of Parkinson’s disease (PD) are widely used for pre-clinical evaluation of novel therapeutics for PD and have provided insights into mechanisms underlying motor dysfunction and nigrostriatal degeneration in PD. Predominantly, magnetic resonance imaging (MRI) studies in such models have focused on alterations in T2 water 1H relaxation or 1H MR spectroscopy (MRS), whilst potential morphological changes and their relationship to histological or behavioural outcomes have not been fully investigated. Identification of MR signal changes that are significantly related to behavioural and histological outcomes in pre-clinical PD models may identify useful non-invasive surrogate markers of nigrostriatal degeneration in vivo. Development of such in vivo imaging-based biomarkers may provide a simple, efficient and comprehensive means to study lesion progression and therapeutic interventions in rodent models of PD, which may also have translational value.

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 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Fearnley, J. M., Lees, A. J. Ageing and Parkinson’s disease: Substantia nigra regional selectivity. Brain 1991;114(Pt 5):2283–2301.

    Article  PubMed  Google Scholar 

  2. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., Goedert, M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839–40.

    Google Scholar 

  3. Brooks, D. J. The role of structural and functional imaging in parkinsonian states with a description of PET technology. Semin Neurol 2008;28:435–445.

    Article  PubMed  Google Scholar 

  4. Reetz, K., Gaser, C., Klein, C. et al. Structural findings in the basal ganglia in genetically determined and idiopathic Parkinson’s disease. Mov Disord 2009;24:99–103.

    Article  PubMed  Google Scholar 

  5. Camicioli, R., Gee, M., Bouchard, T. P. et al. Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism. Parkinsonism Relat Disord 2009;15:187–195.

    Article  PubMed  Google Scholar 

  6. Lewis, M. M., Smith, A. B., Styner, M. et al. Asymmetrical lateral ventricular enlargement in Parkinson’s disease. Eur J Neurol 2009;16:475–481.

    Article  PubMed  CAS  Google Scholar 

  7. Brar, S., Henderson, D., Schenck, J., Zimmerman, E. A. Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism. Arch Neurol 2009;66:371–374.

    Article  PubMed  Google Scholar 

  8. Kosta, P., Argyropoulou, M. I., Markoula, S., Konitsiotis, S. MRI evaluation of the basal ganglia size and iron content in patients with Parkinson’s disease. J Neurol 2006;253:26–32.

    Article  PubMed  Google Scholar 

  9. Martin, W. R., Wieler, M., Gee, M. Midbrain iron content in early Parkinson disease: A potential biomarker of disease status. Neurology 2008;70:1411–1417.

    Article  PubMed  CAS  Google Scholar 

  10. Wallis, L. I., Paley, M. N., Graham, J. M. et al. MRI assessment of basal ganglia iron deposition in Parkinson’s disease. J Magn Reson Imaging 2008;28:1061–1067.

    Article  PubMed  Google Scholar 

  11. Pavese, N., Brooks, D. J. Imaging neurodegeneration in Parkinson’s disease. Biochim Biophys Acta 2009;1792:722–729.

    PubMed  CAS  Google Scholar 

  12. Jenner, P. Functional models of Parkinson’s disease: A valuable tool in the development of novel therapies. Ann Neurol 2008;64(Suppl 2):S16–S29.

    Article  PubMed  CAS  Google Scholar 

  13. Sanchez-Pernaute, R., Brownell, A. L., Jenkins, B. G., Isacson, O. Insights into Parkinson’s disease models and neurotoxicity using non-invasive imaging. Toxicol Appl Pharmacol 2005;207:251–256.

    Article  PubMed  Google Scholar 

  14. Vernon, A. C., Johansson, S. M., Modo, M. M. Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson’s disease. BMC Neurosci 2010;11:1.

    Article  PubMed  Google Scholar 

  15. McNaught, K. S., Bjorklund, L. M., Belizaire, R., Isacson, O., Jenner, P., Olanow, C. W. Proteasome inhibition causes nigral degeneration with inclusion bodies in rats. Neuroreport 2002;13:1437–1441.

    Article  PubMed  CAS  Google Scholar 

  16. Miwa, H., Kubo, T., Suzuki, A., Nishi, K., Kondo, T. Retrograde dopaminergic neuron degeneration following intrastriatal proteasome inhibition. Neurosci Lett 2005;380:93–98.

    Article  PubMed  CAS  Google Scholar 

  17. Deumens, R., Blokland, A., Modeling Parkinson’s, P. J. disease in rats: An evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 2002;175:303–317.

    Article  PubMed  CAS  Google Scholar 

  18. Fornai, F., Lenzi, P., Gesi, M. et al. Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition. J Neurosci 2003;23:8955–8966.

    PubMed  CAS  Google Scholar 

  19. Pan, T., Kondo, S., Zhu, W., Xie, W., Jankovic, J., Le, W. Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement. Neurobiol Dis 2008;32:16–25.

    Article  PubMed  CAS  Google Scholar 

  20. Zhu, W., Xie, W., Pan, T. et al. Prevention and restoration of lactacystin-induced nigrostriatal dopamine neuron degeneration by novel brain-permeable iron chelators. Faseb J 2007;21:3835–3844.

    Article  PubMed  CAS  Google Scholar 

  21. Paxinos, G., Watson, C. The Rat Brain in Stereotaxic Co-ordinates, 6 ed. San Diego, CA: Academic Press; 2007.

    Google Scholar 

  22. Modo, M., Stroemer, R. P., Tang, E., Veizovic, T., Sowniski, P., Hodges, H. Neurological sequelae and long-term behavioural assessment of rats with transient middle cerebral artery occlusion. J Neurosci Methods 2000;104:99–109.

    Article  PubMed  CAS  Google Scholar 

  23. Ungerstedt, U., Arbuthnott, G. W. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 1970;24:485–493.

    Article  PubMed  CAS  Google Scholar 

  24. Sled, J. G., Zijdenbos, A. P., Evans, A. C. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 1998;17(1):87–97.

    Google Scholar 

  25. Vernon, A. C., Zbarsky, V., Datla, K. P., Croucher, M. J., Dexter, D. T. Subtype selective antagonism of substantia nigra pars compacta Group I metabotropic glutamate receptors protects the nigrostriatal system against 6-hydroxydopamine toxicity in vivo. J Neurochem 2007;103:1075–1091.

    Article  PubMed  CAS  Google Scholar 

  26. Vernon, A., Johansson, S. J., Modo, M. M. Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson’s disease. BMC Neuroscience 2009;11:1.

    Article  Google Scholar 

  27. West, M. J., Slomianka, L., Gundersen, H. J. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 1991;231:482–497.

    Article  PubMed  CAS  Google Scholar 

  28. Modo, M., Beech, J. S., Meade, T. J., Williams, S. C., Price, J. A chronic 1 year assessment of MRI contrast agent-labelled neural stem cell transplants in stroke. Neuroimage 2009;47(Suppl 2):T133–T142.

    Article  PubMed  Google Scholar 

  29. Koprich, J. B., Reske-Nielsen, C., Mithal, P., Isacson, O. Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson’s disease. J Neuroinflammation 2008;5:8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Our studies are supported by a grant from the Edmond J. Safra philanthropic foundation, which we thank for their generous financial assistance. We also thank the British Heart Foundation for supporting the 7 T MRI scanner (Preclinical Imaging Unit, Kings College, London). ACV is supported by an Edmond J Safra fellowship. MM is supported by an RCUK fellowship.

Author information

Authors and Affiliations

  1. Department of Neuroscience, Institute of Psychiatry, Centre for the cellular basis of behaviour, The James Black Centre, Kings College London, London, UK

    Anthony C. Vernon

  2. Department of Neuroscience, Kings College London, Institute of Psychiatry, Centre for the Cellular Basis of Behaviour, The James Black Centre, London, UK

    Michel Modo

Authors
  1. Anthony C. Vernon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michel Modo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Modo .

Editor information

Editors and Affiliations

  1. Institute of Psychiatry, Department of Neuroscience, King's College London, Coldharbour Lane 125, London, SE5 9NU, United Kingdom

    Michel Modo

  2. Institute of Cell Engineering, Dept Radiology & Radiological Sciences, Johns Hopkins Univ. Sch. of Med., Rutland Ave. 720, Baltimore, 21205, Maryland, USA

    Jeff W.M. Bulte

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Vernon, A.C., Modo, M. (2011). Non-invasive MR Imaging of Neurodegeneration in a Rodent Model of Parkinson’s Disease. In: Modo, M., Bulte, J. (eds) Magnetic Resonance Neuroimaging. Methods in Molecular Biology, vol 711. Humana Press. https://doi.org/10.1007/978-1-61737-992-5_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-61737-992-5_25

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61737-991-8

  • Online ISBN: 978-1-61737-992-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation