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In Vivo Microdialysis in Parkinson’s Research

  • Giuseppe Di Giovanni
  • Ennio Esposito
  • Vincenzo Di MatteoEmail author
Chapter
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 73)

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.

Keywords

6-OHDA Basal ganglia Free oxygen radicals. Microdialysis MPP+ MPTP Parkinson’s disease ROS 

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

Notes

Acknowledgments

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

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Copyright information

© Springer-Verlag/Wien Printed in Germany 2009

Authors and Affiliations

  • Giuseppe Di Giovanni
    • 2
  • Ennio Esposito
    • 1
  • Vincenzo Di Matteo
    • 1
    Email author
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”Consorzio Mario Negri SudSanta Maria ImbaroItaly
  2. 2.Dipartimento di Medicina SperimentaleSezione di Fisiologia Umana, “G. Pagano”, Universitá degli Studi di PalermoPalermoItaly

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