In vivo microdialysis in Parkinson's research.

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.