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Mesencephalic and extramesencephalic dopaminergic systems in Parkinson’s disease

  • Fanni F. GeiblEmail author
  • Martin T. Henrich
  • Wolfgang H. Oertel
Neurology and Preclinical Neurological Studies - Review Article
  • 144 Downloads

Abstract

Neurodegeneration of the nigrostriatal dopaminergic system and concurrent dopamine (DA) deficiency in the basal ganglia represent core features of Parkinson’s disease (PD). Despite the central role of DA in the pathogenesis of PD, dopaminergic systems outside of the midbrain have not been systematically investigated for Lewy body pathology or neurodegeneration. Dopaminergic neurons show a surprisingly rich neurobiological diversity, suggesting that there is not one general type of dopaminergic neuron, but rather a spectrum of different dopaminergic phenotypes. This heterogeneity on the cellular level could account for the observed differences in susceptibility of the dopaminergic systems to the PD disease process. In this review, we will summarize the long history from the first description of PD to the rationally derived DA replacement therapy, describe the basal neuroanatomical and neuropathological features of the different dopaminergic systems in health and PD, explore how neuroimaging techniques broadened our view of the dysfunctional dopaminergic systems in PD and discuss how dopaminergic replacement therapy ameliorates the classical motor symptoms but simultaneously induces a new set of hyperdopaminergic symptoms.

Keywords

Parkinson disease Dopamine Dopaminergic systems Motor symptoms Dopaminergic therapy l-dopa 

Abbreviations

123I-IBZM

123I-iodobenzamide

18F-FDG

18F-fluorodeoxyglucose

AADC

Aromatic l-amino acid decarboxylase

DA

Dopamine

DAT

Dopamine transporter

ICD

Impulse control disorder

LB

Lewy body

LID

l-dopa-induced dyskinesia

LN

Lewy neurite

MCI

Mild cognitive impairment

MSA

Multiple system atrophy

PD

Parkinson’s disease

PDD

Parkinson’s disease dementia

PSP

Progressive supranuclear palsy

RBD

REM sleep behavior disorder

RRF

Retrorubral field

SN

Substantia nigra

STR

Striatum

TH

Tyrosine hydroxylase

UPDRS

Unified Parkinson’s Disease Rating Scale

VMAT2

Vesicular monoamine transporter 2

VTA

Ventral tegmental area

Notes

Acknowledgements

WHO is supported by the Charitable Hertie Foundation, Frankfurt/Main, Germany. WHO received personal fees for educational talks and/or consultancy, outside of the submitted work, from Abbvie, Adamas, Bristol-Myer-Squibb, Desitin, Mundipharma, Neuropore, Novartis, Roche and UCB Pharma, and grants from the Deutscher Akademischer Austauschdienst, the Deutsche Forschungsgemeinschaft, the International Parkinson-Fonds The Netherlands, the ParkinsonFonds Deutschland, the Michael J. Fox Foundation, USA, the National Research Fond Luxembourg, from Roche International, Switzerland and Novartis Pharma, Germany.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyPhilipps University MarburgMarburgGermany

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