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Long-term retention of neurotoxic ß-carbolines in brain neuromelanin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2003 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 111, no 2, p. 141-157Article in journal (Refereed) Published
Abstract [en]

beta-Carbolines show structural resemblance to the neurotoxic N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and are metabolized to mitochondrial toxicants. Humans are continuously exposed to low levels of beta-carbolines through cooked food, coffee, alcoholic beverages and tobacco smoke. beta-Carbolines have previously been detected in higher levels in the pigmented substantia nigra than in the cortex of humans. The distribution of 3H-labelled harman and norharman in the brain of pigmented and albino mice and in frogs (a species having neuromelanin) was studied by tape-section and light-microscopic autoradiography. Furthermore, the binding of these beta-carbolines to dopamine-melanin and melanin granules from Sepia officinalis was examined. The results revealed a high affinity binding to melanin and a long-term retention (up to 30 days) in pigmented tissues, including neuromelanin-containing neurons of frogs after a single injection. The role of long-term exposure to food-related beta-carbolines and a retention of these compounds in pigment-containing neurons in the induction of idiopathic Parkinson's disease should be further considered.

Place, publisher, year, edition, pages
2003. Vol. 111, no 2, p. 141-157
Keywords [en]
beta-Carbolines, parkinsonism, neuromelanin, harman, norharman, Parkinson's disease, dopamine–melanin, Sepia officinalis
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Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-64767DOI: 10.1007/s00702-003-0080-0PubMedID: 14767717OAI: oai:DiVA.org:uu-64767DiVA, id: diva2:92678
Available from: 2005-05-26 Created: 2005-05-26 Last updated: 2018-01-10Bibliographically approved

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Östergren, ABrittebo, Eva

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