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Related Experiment Videos

VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET.

Raúl De La Fuente-Fernández1, Sarah Furtado, Mark Guttman

  • 1Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, B.C., Canada.

Synapse (New York, N.Y.)
|April 24, 2003
PubMed
Summary
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Dopa-responsive dystonia (DRD) shows increased vesicular monoamine transporter type 2 (VMAT2) binding in the striatum, suggesting compensatory changes. This indicates VMAT2 expression is not directly linked to dopamine synthesis in DRD patients.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Imaging

Background:

  • Dopa-responsive dystonia (DRD) is a lifelong neurological disorder characterized by dopamine deficiency without neuronal loss.
  • This makes DRD an excellent model for studying compensatory mechanisms in response to biochemical abnormalities.

Purpose of the Study:

  • To investigate presynaptic nigrostriatal function and compensatory changes in untreated DRD patients using Positron Emission Tomography (PET).
  • To assess the binding potential of vesicular monoamine transporter type 2 (VMAT2) and dopamine synthesis markers in DRD.

Main Methods:

  • Utilized PET imaging with tracers including (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ), d-threo-[(11)C]methylphenidate ([(11)C]MP), and 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa).
  • Compared tracer binding potentials and uptake rates between untreated DRD patients and healthy controls.

Related Experiment Videos

  • Examined dopamine turnover using [(11)C]raclopride in relation to levodopa treatment in one patient.

    • Main Results:

    • Observed significantly increased [(11)C]DTBZ binding potential in the striatum of DRD patients.
    • Found no significant alterations in [(11)C]MP binding potential or [(18)F]-dopa uptake rate constants.
    • Evidence of increased dopamine turnover was noted in one DRD patient post-levodopa treatment.

    Conclusions:

    • The elevated [(11)C]DTBZ binding in DRD likely reflects reduced intravesicular dopamine concentrations and potential upregulation of VMAT2.
    • Striatal VMAT2 expression, as measured by [(11)C]DTBZ binding, appears independent of dopamine synthesis in DRD.
    • Suggests VMAT2 plays roles beyond dopamine packaging, including cellular protection and monoamine release.