Fumonisin B1-induced increases in neurotransmitter metabolite levels in different brain regions of BALB/c mice.
Fumonisin B1, a toxin produced by Fusarium moniliforme, causes a variety of diseases in animals, including those involving the central nervous system, such as equine leukoencephalomalacia (ELEM). The changes of biogenic amines may reflect fumonisin B1 neurotoxicity. It was previously reported that consumption of feed contaminated with Fusarium moniliforme cultures produced an elevation of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of 5-hydroxytryptamine (5-HT), in whole rat brains. In a subsequent study from the same laboratory, rats given fumonisin B1 orally for 4 weeks showed no changes in neurotransmitter levels of the whole brain. In the current study, groups of five male BALB/c mice were injected with fumonisin B1 subcutaneously at doses of 0, 0.25, 0.75, 2.25, 6.75 mg kg-1 body weight daily for 5 days. One day after the last treatment, their brains were dissected into cerebrum, cerebellum, medulla oblongata, midbrain, corpus striatum and hypothalamus. Levels of norepinephrine (NE), dopamine (DA), DA metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and 5-HT and 5-HIAA were determined. A significant elevation of HVA was observed in mice treated with high doses of fumonisin B1 in most brain regions. In striatum, a decrease of 5-HT was observed by the fumonisin B1 treatment. Ratios of neurotransmitters to metabolites such as HVA/DA and 5-HIAA/5-HT were elevated in several brain regions of the treated groups. An accumulation of neurotransmitter metabolites is suggestive of increased neuronal activity or interference with their efflux from cells.
Tsunoda
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M
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602-7389, USA.
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D037341:Fumonisins; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; C056933:fumonisin B1; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid