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000155689 0247_ $$2doi$$a10.1016/j.nbd.2021.105404
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000155689 041__ $$aEnglish
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000155689 1001_ $$0P:(DE-2719)9000068$$aFauser, Mareike$$b0$$udzne
000155689 245__ $$aSubthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model.
000155689 260__ $$aOrlando, Fla.$$bAcademic Press$$c2021
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000155689 520__ $$aDeep 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.
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000155689 650_7 $$2Other$$a6-hydroxydopamine
000155689 650_7 $$2Other$$aDeep brain stimulation
000155689 650_7 $$2Other$$aDopaminergic neurons
000155689 650_7 $$2Other$$aMesolimbic system
000155689 650_7 $$2Other$$aNeurorestoration
000155689 650_7 $$2Other$$aNigrostriatal system
000155689 650_7 $$2Other$$aParkinson's disease
000155689 650_7 $$2Other$$aSubthalamic nucleus
000155689 650_7 $$2Other$$aVentral tegmental area
000155689 650_2 $$2MeSH$$aAnimals
000155689 650_2 $$2MeSH$$aCorpus Striatum: metabolism
000155689 650_2 $$2MeSH$$aDeep Brain Stimulation: methods
000155689 650_2 $$2MeSH$$aDopaminergic Neurons: metabolism
000155689 650_2 $$2MeSH$$aFemale
000155689 650_2 $$2MeSH$$aLimbic System: metabolism
000155689 650_2 $$2MeSH$$aMale
000155689 650_2 $$2MeSH$$aOxidopamine: toxicity
000155689 650_2 $$2MeSH$$aParkinsonian Disorders: chemically induced
000155689 650_2 $$2MeSH$$aParkinsonian Disorders: metabolism
000155689 650_2 $$2MeSH$$aParkinsonian Disorders: therapy
000155689 650_2 $$2MeSH$$aRats
000155689 650_2 $$2MeSH$$aRats, Wistar
000155689 650_2 $$2MeSH$$aSubstantia Nigra: metabolism
000155689 650_2 $$2MeSH$$aSubthalamic Nucleus: metabolism
000155689 650_2 $$2MeSH$$aTyrosine 3-Monooxygenase: metabolism
000155689 650_2 $$2MeSH$$aVentral Tegmental Area: metabolism
000155689 7001_ $$aRicken, Manuel$$b1
000155689 7001_ $$aMarkert, Franz$$b2
000155689 7001_ $$aWeis, Nikolai$$b3
000155689 7001_ $$aSchmitt, Oliver$$b4
000155689 7001_ $$aGimsa, Jan$$b5
000155689 7001_ $$aWinter, Christine$$b6
000155689 7001_ $$aBadstübner-Meeske, Kathrin$$b7
000155689 7001_ $$0P:(DE-2719)9000306$$aStorch, Alexander$$b8$$eLast author$$udzne
000155689 773__ $$0PERI:(DE-600)1471408-5$$a10.1016/j.nbd.2021.105404$$gVol. 156, p. 105404 -$$p105404$$tNeurobiology of disease$$v156$$x0969-9961$$y2021
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