TY  - JOUR
AU  - Fauser, Mareike
AU  - Ricken, Manuel
AU  - Markert, Franz
AU  - Weis, Nikolai
AU  - Schmitt, Oliver
AU  - Gimsa, Jan
AU  - Winter, Christine
AU  - Badstübner-Meeske, Kathrin
AU  - Storch, Alexander
TI  - Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model.
JO  - Neurobiology of disease
VL  - 156
SN  - 0969-9961
CY  - Orlando, Fla.
PB  - Academic Press
M1  - DZNE-2021-00857
SP  - 105404
PY  - 2021
AB  - 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.
KW  - Animals
KW  - Corpus Striatum: metabolism
KW  - Deep Brain Stimulation: methods
KW  - Dopaminergic Neurons: metabolism
KW  - Female
KW  - Limbic System: metabolism
KW  - Male
KW  - Oxidopamine: toxicity
KW  - Parkinsonian Disorders: chemically induced
KW  - Parkinsonian Disorders: metabolism
KW  - Parkinsonian Disorders: therapy
KW  - Rats
KW  - Rats, Wistar
KW  - Substantia Nigra: metabolism
KW  - Subthalamic Nucleus: metabolism
KW  - Tyrosine 3-Monooxygenase: metabolism
KW  - Ventral Tegmental Area: metabolism
KW  - 6-hydroxydopamine (Other)
KW  - Deep brain stimulation (Other)
KW  - Dopaminergic neurons (Other)
KW  - Mesolimbic system (Other)
KW  - Neurorestoration (Other)
KW  - Nigrostriatal system (Other)
KW  - Parkinson's disease (Other)
KW  - Subthalamic nucleus (Other)
KW  - Ventral tegmental area (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34044146
DO  - DOI:10.1016/j.nbd.2021.105404
UR  - https://pub.dzne.de/record/155689
ER  -