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Neurotoxic effect of maneb in rats as studied by neurochemical and immunohistochemical parameters
Brian Svend Nielsen1, Erik H Larsen, Ole Ladefoged
1The Danish Institute for Food and Veterinary Research (DFVF), Department of Toxicology and Risk Assessment, DK-2860 Søborg, Denmark.
Abstract:
Epidemiological investigations document that workers in agriculture, horticulture and people living near areas with frequent use of pesticides have increased risk of developing symptoms of Parkinson's disease. This study investigated the neurotoxic effect of the fungicide maneb by morphological, immunohistochemical and neurochemical methods applying young Sprague-Dawley male rat as the model. Intraperitoneal dosing (7.5, 15 or 30mg maneb/kg bodyweight/week for 12 weeks) demonstrated dose-related increased manganese concentration in corpus striatum. The striatal concentration of 5-hydroxytryptamine (5-HT) increased in a dose-related manner, as did the 5-HT concentrations in the rest of the brain indicating early sign of neurotoxicity. Striatal acetylcholinesterase activity was not affected. The concentrations of noradrenaline, dopamine, neurotransmitter amino acids and the levels of the proteins α-synuclein and synaptophysin in corpus striatum and the rest of the brain were not changed. No histological parameter was affected when studied in corpus striatum and substantia nigra.
Insights
Exposure to the fungicide maneb in rats increased manganese and serotonin levels in the brain, suggesting early neurotoxicity. This fungicide may pose risks to agricultural workers, potentially contributing to Parkinson
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Pesticide exposure is linked to increased Parkinson's disease risk in agricultural workers.
- Fungicides like maneb are widely used, necessitating investigation into their neurotoxic potential.
Purpose of the Study:
- To investigate the neurotoxic effects of the fungicide maneb in a rat model.
- To assess the impact of maneb on specific neurochemical and morphological parameters.
Main Methods:
- Young Sprague-Dawley male rats were administered intraperitoneal injections of maneb (7.5, 15, or 30 mg/kg) weekly for 12 weeks.
- Neurotoxicity was evaluated using morphological, immunohistochemical, and neurochemical analyses.
- Manganese concentration, neurotransmitter levels (5-HT, noradrenaline, dopamine), amino acids, acetylcholinesterase activity, and protein levels (α-synuclein, synaptophysin) were measured.
Main Results:
- Dose-dependent increases in manganese concentration were observed in the corpus striatum.
- A dose-dependent increase in 5-hydroxytryptamine (5-HT) levels was noted in both the striatum and the rest of the brain, indicating early neurotoxicity.
- No significant changes were found in striatal acetylcholinesterase activity, dopamine, noradrenaline, amino acids, α-synuclein, or synaptophysin levels.
- No histological alterations were observed in the corpus striatum or substantia nigra.
Conclusions:
- Maneb exposure leads to increased manganese and serotonin levels in rat brains, suggesting potential early neurotoxic effects.
- While not affecting all measured parameters, the observed changes warrant further investigation into the long-term neurological consequences of maneb exposure.
- Findings highlight the need for caution regarding occupational exposure to maneb, particularly for individuals in agricultural settings.
