Journal Article

DZNE-2021-00857

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model.

Fauser, M.Extern* ; Ricken, M. ; Markert, F. ; Weis, N. ; Schmitt, O. ; Gimsa, J. ; Winter, C. ; Badstübner-Meeske, K. ; Storch, A. (Last author)DZNE*

2021
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.nbd.2021.105404

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.

Keyword(s): Animals (MeSH) ; Corpus Striatum: metabolism (MeSH) ; Deep Brain Stimulation: methods (MeSH) ; Dopaminergic Neurons: metabolism (MeSH) ; Female (MeSH) ; Limbic System: metabolism (MeSH) ; Male (MeSH) ; Oxidopamine: toxicity (MeSH) ; Parkinsonian Disorders: chemically induced (MeSH) ; Parkinsonian Disorders: metabolism (MeSH) ; Parkinsonian Disorders: therapy (MeSH) ; Rats (MeSH) ; Rats, Wistar (MeSH) ; Substantia Nigra: metabolism (MeSH) ; Subthalamic Nucleus: metabolism (MeSH) ; Tyrosine 3-Monooxygenase: metabolism (MeSH) ; Ventral Tegmental Area: metabolism (MeSH) ; 6-hydroxydopamine ; Deep brain stimulation ; Dopaminergic neurons ; Mesolimbic system ; Neurorestoration ; Nigrostriatal system ; Parkinson's disease ; Subthalamic nucleus ; Ventral tegmental area

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Contributing Institute(s):

1. Non-Motor Symptoms in Parkinson's disease (AG Storch 2 Rostock)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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