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Mesencephalic and extramesencephalic dopaminergic systems in Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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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.

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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

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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.

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  1. Department of Neurology, Philipps University Marburg, Baldingerstraße 1, 35043, Marburg, Germany

    Fanni F. Geibl, Martin T. Henrich & Wolfgang H. Oertel

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Geibl, F.F., Henrich, M.T. & Oertel, W.H. Mesencephalic and extramesencephalic dopaminergic systems in Parkinson’s disease. J Neural Transm 126, 377–396 (2019). https://doi.org/10.1007/s00702-019-01970-9

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