Home > Publications Database > Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model. > print

001     155689
005     20230915092336.0
024 7 _ |a 10.1016/j.nbd.2021.105404
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024 7 _ |a pmid:34044146
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024 7 _ |a 0969-9961
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024 7 _ |a 1095-953X
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037 _ _ |a DZNE-2021-00857
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Fauser, Mareike
|0 P:(DE-2719)9000068
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245 _ _ |a Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model.
260 _ _ |a Orlando, Fla.
|c 2021
|b Academic Press
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520 _ _ |a 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.
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650 _ 7 |a 6-hydroxydopamine
|2 Other
650 _ 7 |a Deep brain stimulation
|2 Other
650 _ 7 |a Dopaminergic neurons
|2 Other
650 _ 7 |a Mesolimbic system
|2 Other
650 _ 7 |a Neurorestoration
|2 Other
650 _ 7 |a Nigrostriatal system
|2 Other
650 _ 7 |a Parkinson's disease
|2 Other
650 _ 7 |a Subthalamic nucleus
|2 Other
650 _ 7 |a Ventral tegmental area
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Corpus Striatum: metabolism
|2 MeSH
650 _ 2 |a Deep Brain Stimulation: methods
|2 MeSH
650 _ 2 |a Dopaminergic Neurons: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Limbic System: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Oxidopamine: toxicity
|2 MeSH
650 _ 2 |a Parkinsonian Disorders: chemically induced
|2 MeSH
650 _ 2 |a Parkinsonian Disorders: metabolism
|2 MeSH
650 _ 2 |a Parkinsonian Disorders: therapy
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Rats, Wistar
|2 MeSH
650 _ 2 |a Substantia Nigra: metabolism
|2 MeSH
650 _ 2 |a Subthalamic Nucleus: metabolism
|2 MeSH
650 _ 2 |a Tyrosine 3-Monooxygenase: metabolism
|2 MeSH
650 _ 2 |a Ventral Tegmental Area: metabolism
|2 MeSH
700 1 _ |a Ricken, Manuel
|b 1
700 1 _ |a Markert, Franz
|b 2
700 1 _ |a Weis, Nikolai
|b 3
700 1 _ |a Schmitt, Oliver
|b 4
700 1 _ |a Gimsa, Jan
|b 5
700 1 _ |a Winter, Christine
|b 6
700 1 _ |a Badstübner-Meeske, Kathrin
|b 7
700 1 _ |a Storch, Alexander
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773 _ _ |a 10.1016/j.nbd.2021.105404
|g Vol. 156, p. 105404 -
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|t Neurobiology of disease
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|y 2021
|x 0969-9961
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