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@ARTICLE{Depboylu:137775,
      author       = {Depboylu, Candan and Maurer, Lukas and Matusch, Andreas and
                      Hermanns, Guido and Windolph, Andrea and Béhé, Martin and
                      Oertel, Wolfgang H. and Höglinger, Günter U.},
      title        = {{E}ffect of long-term treatment with pramipexole or
                      levodopa on presynaptic markers assessed by longitudinal
                      [123{I}]{FP}-{CIT} {SPECT} and histochemistry},
      journal      = {NeuroImage},
      volume       = {79},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2013-04091},
      pages        = {191 - 200},
      year         = {2013},
      abstract     = {A previous clinical trial studied the effect of long-term
                      treatment with levodopa (LD) or the dopamine agonist
                      pramipexole (PPX) on disease progression in Parkinson
                      disease using SPECT with the dopamine transporter
                      (DAT)-radioligand [(123)I]β-CIT as surrogate marker.
                      [(123)I]β-CIT binding declined to significantly lower
                      levels in patients receiving LD compared to PPX. However,
                      the interpretation of this difference as LD-induced
                      neurotoxicity, PPX-induced neuroprotection/-regeneration, or
                      only drug-induced regulatory changes of DAT-availability
                      remained controversial. To address this question
                      experimentally, we induced a subtotal lesion of the
                      substantia nigra in mice by bilateral injection of the
                      neurotoxin 6-hydroxydopamine. After 4 weeks, mice were
                      treated for 20 weeks orally with LD (100mg/kg/day) or PPX
                      (3mg/kg/day), or water (vehicle) only. The integrity of
                      nigrostriatal projections was assessed by repeated
                      [(123)I]FP-CIT SPECT in vivo and by immunostaining for DAT
                      and the dopamine-synthesizing enzyme tyrosine hydroxylase
                      (TH) after sacrifice. In sham-lesioned mice, we found that
                      both LD and PPX treatment significantly decreased the
                      striatal FP-CIT binding (LD: $-21\%;$ PPX: $-14\%)$ and
                      TH-immunoreactivity (LD: $-42\%;$ PPX: $-45\%),$ but
                      increased DAT-immunoreactivity (LD: $+42\%;$ PPX: $+33\%)$
                      compared to controls without dopaminergic treatment. In
                      6-hydroxydopamine-lesioned mice, however, neither LD nor PPX
                      significantly influenced the stably reduced FP-CIT SPECT
                      signal (LD: $-66\%;$ PPX: $-66\%;$ controls $-66\%),$
                      TH-immunoreactivity (LD: $-70\%;$ PPX: $-72\%;$ controls:
                      $-77\%)$ and DAT-immunoreactivity (LD: $-70\%;$ PPX:
                      $-75\%;$ controls: $-75\%)$ in the striatum or the number of
                      TH-positive cells in the substantia nigra (LD: $-88\%;$ PPX:
                      $-88\%;$ controls: $-86\%),$ compared to lesioned mice
                      without dopaminergic treatment. In conclusion, chronic
                      dopaminergic stimulation with LD or PPX induced similar
                      adaptive presynaptic changes in healthy mice, but no
                      discernible changes in severely lesioned mice. These
                      findings allow to more reliably interpret the results from
                      clinical trials using neuroimaging of DAT as surrogate
                      parameter. Copyright © 2013 Elsevier Inc. All rights
                      reserved.},
      cin          = {INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-2-20090406},
      pnm          = {333 - Pathophysiological Mechanisms of Neurological and
                      Psychiatric Diseases (POF2-333)},
      pid          = {G:(DE-HGF)POF2-333},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000320412200020},
      doi          = {10.1016/j.neuroimage.2013.04.076},
      url          = {https://juser.fz-juelich.de/record/137775},
}