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Handbook of Neurotoxicity pp 753–788Cite as

Dopaminergic Neurons in Parkinson’s Disease

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Abstract

The discovery of dopamine as a brain neurotransmitter by Arvid Carlsson and colleagues about 50 years ago contributed to better understand some of the brain diseases. Some of the drugs that are most widely used in neurologic and psychiatry illnesses, such as levodopa and antipsychotic drugs, act on dopaminergic mechanism. The discovery that the motor impairments of Parkinson’s disease patients improved after restoring the physiological levels of striatal dopamine with levodopa attracted the attention of the neuroscience community for the role of this neurotransmitter in motor and brain functions. In the last decades, the knowledge has also been challenged by evidence that Parkinson’s disease also affects cognitive and affective functions. Shortly after the introduction of levodopa as a therapy, a complex set of secondary phenomena such as dyskinesia was observed following repeated administration of the dopamine precursor. Information of dopaminergic cells and circuits has been enriched by findings obtained with several and highly sensitive technology in cellular biology, with sophisticated behavioral analyses of transgenic animals and functional neuroimaging. The present chapter attempts to review results reported in different clinical studies and animal models to provide a comprehensive picture of the role of dopamine in Parkinson’s disease. Treatments have successfully been translated from preclinical to pharmacotherapeutic arsenal increasing clinical settings.

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Abbreviations

3-OMD:

3-O-methyldopa

6-OHDA:

6-hydroxydopamine

AIMs:

Abnormal involuntary movements

AS:

Alpha-synuclein

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

DARPP-32:

Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa

DAT:

Dopamine transporter

DLB:

Dementia with Lewy body

DMV:

Dorsal motor nucleus of vagus

DYN:

Dynorphin

ENK:

Enkephalin

FS:

Fast spiking

GPCRs:

G protein-coupled receptors

GPe:

External segment of the globus pallidus

GPi:

Internal segment of the globus pallidus

iLBP:

Incident Lewy body pathology

IrtZ:

Intermediate reticular zone

i.v.:

Intravenous

LB:

Lewy bodies

LC:

Locus coeruleus

L-DOPA:

L-3,4-dihydroxyphenylalanine

LN:

Lewy neurites

LTS:

Low-threshold spiking

MAO-B:

Monoamine oxidase-B

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MSN:

Medium spiny neuron

NPY:

Neuropeptide Y

PD:

Parkinson’s disease

PET:

Positive emission tomography

PV:

Parvalbumin

SN:

Substantia nigra

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

SOM:

Somatostatin

SP:

Substance P

SPECT:

Single-photon emission computed tomography

STN:

Subthalamic nucleus

TH:

Tyrosine hydroxylase

VMAT2:

Vesicular monoamine transporter 2

VTA:

Ventral tegmental area

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Acknowledgments

This work was partially supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico (CNPQ), Coordenadoria de Aperfeiçoamento de Pessoal (CAPES), Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC), CAPES-COFECUB (France/Brazil; 681/2010), FAPESP/INSERM (2008/55092-9), and CAPES/CNPq/FAPs – Linha Pesquisador Visitante Especial/Programa Especial de Cooperacao Internacional/PECI (402658/2012-4). The other authors have no financial or personal conflict of interest related to this study. The authors are grateful to Majid Amar for the preparation of Fig. 2 and to Célia Ap. da Silva and Laure Ginestet for the helpful technical support. We would like to thank MSc Fernando Padovan Neto, MSc Danielle Oliveira Tavares, PhD Roberta Cavalcanti Kwiatkoski, and PhD Nádia Rúbia Ferreira.

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Authors and Affiliations

  1. INSERM UMR 975 (ex U679), CNRS UMR 7225, Université Pierre et Marie Curie (UPMC), Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière (CRICM), Thérapeutique Expérimentale de la neurodégénérescence, Hôpital de la Salpêtrière, 47 boulevard de l’Hôpital, 75651, Paris, France

    Rita Raisman-Vozari

  2. Departamento MFP-Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo (USP), Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), Ribeirão Preto, SP, Brazil

    Mariza Bortolanza, Ana Carolina de Castro Issy & Elaine Del Bel

  3. Laboratório Experimental de Doenças Neurodegenerativas, Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil

    Rui Daniel Prediger

  4. Department of Neurosciences and Behavior Sciences, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil

    Bruno Lopes dos Santos

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  1. Rui Daniel Prediger
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  2. Mariza Bortolanza
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  3. Ana Carolina de Castro Issy
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  4. Bruno Lopes dos Santos
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  5. Elaine Del Bel
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  6. Rita Raisman-Vozari
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Correspondence to Rita Raisman-Vozari .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Prediger, R.D., Bortolanza, M., de Castro Issy, A.C., dos Santos, B.L., Del Bel, E., Raisman-Vozari, R. (2014). Dopaminergic Neurons in Parkinson’s Disease. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_7

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