Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.


: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.


J Neurochem


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 M





Has Abstract


2004-01-01 00:00:00














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  • The monoamine neurons of the rat brain preferentially express a splice variant of alpha1B subunit of the N-type calcium channel.

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    authors: Minieri L,Pivonkova H,Harantova L,Anderova M,Ferroni S

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    authors: Janowsky A,Steranka LR,Gillespie DD,Sulser F

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    pub_type: 杂志文章


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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Wales SQ,Li B,Laing JM,Aurelian L

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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Rothstein JD,Kuncl RW

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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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    更新日期:1993-04-01 00:00:00