%0 Journal Article
%A Fauser, Mareike
%A Ricken, Manuel
%A Markert, Franz
%A Weis, Nikolai
%A Schmitt, Oliver
%A Gimsa, Jan
%A Winter, Christine
%A Badstübner-Meeske, Kathrin
%A Storch, Alexander
%T Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model.
%J Neurobiology of disease
%V 156
%@ 0969-9961
%C Orlando, Fla.
%I Academic Press
%M DZNE-2021-00857
%P 105404
%D 2021
%X 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.
%K Animals
%K Corpus Striatum: metabolism
%K Deep Brain Stimulation: methods
%K Dopaminergic Neurons: metabolism
%K Female
%K Limbic System: metabolism
%K Male
%K Oxidopamine: toxicity
%K Parkinsonian Disorders: chemically induced
%K Parkinsonian Disorders: metabolism
%K Parkinsonian Disorders: therapy
%K Rats
%K Rats, Wistar
%K Substantia Nigra: metabolism
%K Subthalamic Nucleus: metabolism
%K Tyrosine 3-Monooxygenase: metabolism
%K Ventral Tegmental Area: metabolism
%K 6-hydroxydopamine (Other)
%K Deep brain stimulation (Other)
%K Dopaminergic neurons (Other)
%K Mesolimbic system (Other)
%K Neurorestoration (Other)
%K Nigrostriatal system (Other)
%K Parkinson's disease (Other)
%K Subthalamic nucleus (Other)
%K Ventral tegmental area (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34044146
%R 10.1016/j.nbd.2021.105404
%U https://pub.dzne.de/record/155689