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@ARTICLE{Fauser:155689,
      author       = {Fauser, Mareike and Ricken, Manuel and Markert, Franz and
                      Weis, Nikolai and Schmitt, Oliver and Gimsa, Jan and Winter,
                      Christine and Badstübner-Meeske, Kathrin and Storch,
                      Alexander},
      title        = {{S}ubthalamic nucleus deep brain stimulation induces
                      sustained neurorestoration in the mesolimbic dopaminergic
                      system in a {P}arkinson's disease model.},
      journal      = {Neurobiology of disease},
      volume       = {156},
      issn         = {0969-9961},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {DZNE-2021-00857},
      pages        = {105404},
      year         = {2021},
      abstract     = {Deep brain stimulation (DBS) of the subthalamic nucleus
                      (STN) is an established therapeutic principle in Parkinson's
                      disease, but the underlying mechanisms, particularly
                      mediating non-motor actions, remain largely enigmatic.The
                      delayed onset of neuropsychiatric actions in conjunction
                      with first experimental evidence that STN-DBS causes
                      disease-modifying effects prompted our investigation on how
                      cellular plasticity in midbrain dopaminergic systems is
                      affected by STN-DBS.We applied unilateral or bilateral
                      STN-DBS in two independent cohorts of 6-hydroxydopamine
                      hemiparkinsonian rats four to eight weeks after dopaminergic
                      lesioning to allow for the development of a stable
                      dopaminergic dysfunction prior to DBS electrode
                      implantation.After 5 weeks of STN-DBS, stimulated animals
                      had significantly more TH+ dopaminergic neurons and fibres
                      in both the nigrostriatal and the mesolimbic systems
                      compared to sham controls with large effect sizes of
                      gHedges = 1.9-3.4. DBS of the entopeduncular nucleus as
                      the homologue of the human Globus pallidus internus did not
                      alter the dopaminergic systems. STN-DBS effects on
                      mesolimbic dopaminergic neurons were largely confirmed in an
                      independent animal cohort with unilateral STN stimulation
                      for 6 weeks or for 3 weeks followed by a 3 weeks washout
                      period. The latter subgroup even demonstrated persistent
                      mesolimbic dopaminergic plasticity after washout. Pilot
                      behavioural testing showed that augmentative dopaminergic
                      effects on the mesolimbic system by STN-DBS might translate
                      into improvement of sensorimotor neglect.Our data support
                      sustained neurorestorative effects of STN-DBS not only in
                      the nigrostriatal but also in the mesolimbic system as a
                      potential factor mediating long-latency neuropsychiatric
                      effects of STN-DBS in Parkinson's disease.},
      keywords     = {Animals / Corpus Striatum: metabolism / Deep Brain
                      Stimulation: methods / Dopaminergic Neurons: metabolism /
                      Female / Limbic System: metabolism / Male / Oxidopamine:
                      toxicity / Parkinsonian Disorders: chemically induced /
                      Parkinsonian Disorders: metabolism / Parkinsonian Disorders:
                      therapy / Rats / Rats, Wistar / Substantia Nigra: metabolism
                      / Subthalamic Nucleus: metabolism / Tyrosine
                      3-Monooxygenase: metabolism / Ventral Tegmental Area:
                      metabolism / 6-hydroxydopamine (Other) / Deep brain
                      stimulation (Other) / Dopaminergic neurons (Other) /
                      Mesolimbic system (Other) / Neurorestoration (Other) /
                      Nigrostriatal system (Other) / Parkinson's disease (Other) /
                      Subthalamic nucleus (Other) / Ventral tegmental area
                      (Other)},
      cin          = {AG Storch 2 Rostock},
      ddc          = {570},
      cid          = {I:(DE-2719)5000014},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34044146},
      doi          = {10.1016/j.nbd.2021.105404},
      url          = {https://pub.dzne.de/record/155689},
}