Nigral Degeneration in Animal Models of Multiple System Atrophy
L-DOPA unresponsive parkinsonism is widely considered the predominant motor disorder of multiple system atrophy (MSA). The neuropathological changes underlying MSA-associated parkinsonism are dominated by neuronal fall out in anatomically related nigral and striatal pathways including afferent projections arising from the caudolateral substantia nigra pars compacta (SNpc) and efferent striatopallidal projections originating in the dorsolateral posterior putamen (striatonigral degeneration SND). The characteristic lesion pattern of SND can be replicated in rats by a double toxin double lesion approach that requires sequential stereotaxic injections of a nigral (e.g. 6-hydroxydopamine; 6-OHDA) and a striatal neurotoxin (e.g. quinolinic acid; QA) into the medial forebrain bundle (MFB) and ipsilateral striatum, respectively (Wenning et al., 1996, 1999a). Immunohistochemical analysis in the double toxin double lesion MSA-SND model reveals characteristic changes with more than 90% loss of tyrosine hydroxylase positive (TH) neurons in the SNpc and more than 70% loss of striatal cross-sectional surface area. In addition to the double toxin double lesion model a single toxin double lesion approach has been proposed using mitochondrial respiratory chain (MRC) inhibitors such as 3-nitropropionic acid (3-NP) or l-methyl-4-phenyl-l,2,3,6 tetrahydropyridine (MPTP) (Wenning et al., 2000).
KeywordsTyrosine Hydroxylase Multiple System Atrophy Mitochondrial Respiratory Chain Quinolinic Acid Medial Forebrain Bundle
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