Elsevier

Experimental Neurology

Volume 177, Issue 2, October 2002, Pages 453-460
Experimental Neurology

Regular Article
Neuroinvasive Nocardia asteroides GUH-2 Induces Apoptosis in the Substantia Nigra in Vivo and Dopaminergic Cells in Vitro

https://doi.org/10.1006/exnr.2002.8012Get rights and content

Abstract

Neurodegenerative diseases such as Parkinson's disease are increasingly prevalent in the aging population worldwide. The causes of these disorders are unknown, but many studies have suggested that the etiology is likely multifactorial and may involve exposure to something in the environment combined with the normal aging process. Nocardia asteroides are bacteria commonly found in the soil, and neuroinvasive strains of nocardiae have been described. N. asteroides strain GUH-2 invades the brains of experimentally infected animals and selectively affects dopaminergic neurons of the substantia nigra (SN), causing an l-DOPA-responsive movement disorder resembling parkinsonism. Furthermore, dopaminergic neurons undergo morphological changes characteristic of apoptosis following nocardial infection. Apoptosis has been implicated in dopaminergic neuronal dropout in Parkinson's patients as well as other parkinsonian models. Thus, in this study, in vivo and in vitro models were utilized to measure the ability of GUH-2 to induce the apoptotic death of dopaminergic cells. Following infection with GUH-2, dopaminergic apoptotic cells were identified in the SN of animals by in situ end labeling, which detects DNA fragmentation, combined with fluorescent immunolabeling of tyrosine hydroxylase-positive cells. In addition, apoptosis was observed in PC12 cell cultures incubated with GUH-2 by both in situ end labeling and the annexin V assay, which detects externalization of phosphatidylserine of the plasma membrane, indicating apoptotic death. Based on the results of these studies, it appears that experimental infection with N. asteroides provides a general model for studying apoptosis in parkinsonian disorders.

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      However, with increasing doses, these resulted in increased mortality of mice [5,13]. Although descriptions of abnormal murine behavior following cerebral nocardial infections were reported [5–13], no photographic evidence showing this movement disorder was ever published. A blinded study was initiated to determine whether or not dopamine depletion correlated with the development of movement disorders in nocardiae-infected mice, with emphasis on animals that exhibited head tremors.

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