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In Vivo Microdialysis in Parkinson’s Research

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Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 73))

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopamine (DA) neurons in the nigrostriatal system, which in turn produces profound neurochemical changes within the basal ganglia, representing the neural substrate for parkinsonian motor symptoms. The pathogenesis of the disease is still not completely understood, but environmental and genetic factors are thought to play important roles. Research into the pathogenesis and the development of new therapeutic intervention strategies that will slow or stop the progression of the disease in human has rapidly advanced by the use of neurotoxins that specifically target DA neurons. Over the years, a broad variety of experimental models of the disease has been developed and applied in diverse animal species. The two most common toxin models used employ 6-hydroxydopamine (6-OHDA) and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4- phenilpyridinium ion (MPTP/MPP+), either given systemically or locally applied into the nigrostriatal pathway, to resemble PD features in animals. Both neurotoxins selectively and rapidly destroy catecolaminergic neurons, although with different mechanisms. Since in vivo microdialysis coupled to high-performance liquid chromatography is an established technique for studying physiological, pharmacological, and pathological changes of a wide range of low molecular weight substances in the brain extracellular fluid, here we review the most prominent animal and human data obtained by the use of this technique in PD research.

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Abbreviations

.OH:

Hydroxyl radicals

1O2 :

singlet oxygen

2-HBA:

Salicylate

4-HBA:

4-hydroxybenzoic acid

5-HIAA:

5-hydroxyindoleacetic acid

6-OHDA:

6-hydroxydopamine

7-NI:

7-Nitroindazole

A2A :

Adenosine2A

ACE:

Angiotensin II converting enzyme

BDNF:

Brain-derived neurotrophic factor

COX:

Cyclooxygenase

D3 :

calcitriol

DA:

Dopamine

DAT:

DA transporter

DBS:

Deep brain stimulation

DOPAC:

3,4-dihydroxyphenyl acetic acid

ESC:

Embryonic stem cells

GDNF:

Glial cell line-derived neurotrophic factor

GLU:

Glutamate

GPe:

Globus pallidus external segment

GPi:

Globus pallidus internal segment

GSH:

Glutathione

GSSG:

Glutathione disulfide

HPLC:

High performance liquid chromatography

HVA:

Homovanillic acid

iNOS:

Inducible nitric oxide synthase

LDL:

Low-density lipoprotein

L-DOPA:

L-3,4-dihydroxyphenylalanine

L-NAME:

N (G)-nitro-L- arginine methyl ester

MAO:

Monoamine oxidases

MPP+:

1-methyl-4-phenilpyridinium ion

MPTP:

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

MSC:

mesenchymal stem cells

NMDA:

N-methyl-D-aspartate

nNOS:

neuronal Nitric oxide synthase

NOP:

Nociceptin/orfanin FQ

O2 − :

Superoxide anions

ONOO− :

Peroxynitrite

PARP:

Poly (ADP-ribose) polymerase

PD:

Parkinson's disease

ROS:

Reactive oxygen species

SMA:

Supplementary motor cortex

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

SOD:

Superoxide dismutase

STN:

Subthalamic nucleus

STN-HFS:

High-frequency stimulation of the subthalamic nucleus

TH:

Tyrosine hydroxylase

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Acknowledgments

The authors thank Ms. Barbara Mariani for her help in preparing the manuscript.

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  1. Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio Mario Negri Sud, 66030, Santa Maria Imbaro, CH, Italy

    Ennio Esposito & Vincenzo Di Matteo

  2. Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana, “G. Pagano”, Universitá degli Studi di Palermo, 90134, Palermo, Italy

    Giuseppe Di Giovanni

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  1. Giuseppe Di Giovanni
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  1. Fac. Medicina e Chirurgia, Università di Palermo, Corso Tukory 129, Palermo, 90134, Italy

    Giuseppe Giovanni

  2. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Vincenzo Di Matteo

  3. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Ennio Esposito

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Di Giovanni, G., Esposito, E., Di Matteo, V. (2009). In Vivo Microdialysis in Parkinson’s Research. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_18

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