Abstract:
:In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neurones in the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Champy P,Höglinger GU,Féger J,Gleye C,Hocquemiller R,Laurens A,Guérineau V,Laprévote O,Medja F,Lombès A,Michel PP,Lannuzel A,Hirsch EC,Ruberg Mdoi
10.1046/j.1471-4159.2003.02138.xkeywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
63-9issue
1eissn
0022-3042issn
1471-4159pii
2138journal_volume
88pub_type
杂志文章abstract::Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate for...
journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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doi:10.1111/j.1471-4159.1987.tb05599.x
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doi:10.1111/j.1471-4159.2008.05518.x
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doi:10.1111/j.1471-4159.1986.tb12945.x
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doi:10.1111/j.1471-4159.1993.tb05845.x
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abstract::Abstract Huntingtin is a large, multi-domain protein of unknown function in the brain. An abnormally elongated polyglutamine stretch in its N-terminus causes Huntington's disease (HD), a progressive neurodegenerative disorder. Huntingtin has been proposed to play a functional role in membrane trafficking via proteins ...
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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doi:10.1046/j.1471-4159.1994.62020788.x
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb08914.x
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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doi:10.1111/j.1471-4159.1984.tb09729.x
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:2001-05-01 00:00:00