A zebrafish model of manganism reveals reversible and treatable symptoms independent of neurotoxicity

Abstract Manganese (Mn) is essential for neuronal function, yet toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson’s disease (PD). However, manganism is di...

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Published inDisease models & mechanisms
Main Authors Bakthavatsalam, Subha, Das Sharma, Shreya, Sonawane, Mahendra, Thirumalai, Vatsala, Datta, Ankona
Format Journal Article
LanguageEnglish
Published 01.01.2014
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Abstract Abstract Manganese (Mn) is essential for neuronal function, yet toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson’s disease (PD). However, manganism is distinct from PD and the neural basis of its pathology is poorly understood. To address this issue, we generated a zebrafish model of manganism by incubating larvae in rearing medium containing Mn. We find that Mn-treated zebrafish larvae exhibit specific postural and locomotor defects. Larvae begin to float on their sides, show a curved spine, and swim in circles. We discovered that Mn-treatment causes postural defects by interfering with mechanotransduction at the neuromasts. Furthermore, we find that the circling locomotion could be caused by long duration bursting in the motor neurons, which can lead to long duration tail bends in the Mn-treated larvae. Mn-treated larvae also exhibited fewer startle movements. Additionally, we show that the intensity of tyrosine hydroxylase immunoreactivity is reversibly reduced after Mn-treatment. This led us to propose that reduced dopamine neuromodulation could drive the changes in startle movements. To test this, when we supplemented dopamine to Mn-treated larvae, the larvae exhibited normal number of startle swims. Taken together, these results indicate that Mn interferes with neuronal function at the sensory, motor, and modulatory levels, and open avenues for therapeutically targeted studies on the zebrafish model of manganism.
AbstractList Abstract Manganese (Mn) is essential for neuronal function, yet toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson’s disease (PD). However, manganism is distinct from PD and the neural basis of its pathology is poorly understood. To address this issue, we generated a zebrafish model of manganism by incubating larvae in rearing medium containing Mn. We find that Mn-treated zebrafish larvae exhibit specific postural and locomotor defects. Larvae begin to float on their sides, show a curved spine, and swim in circles. We discovered that Mn-treatment causes postural defects by interfering with mechanotransduction at the neuromasts. Furthermore, we find that the circling locomotion could be caused by long duration bursting in the motor neurons, which can lead to long duration tail bends in the Mn-treated larvae. Mn-treated larvae also exhibited fewer startle movements. Additionally, we show that the intensity of tyrosine hydroxylase immunoreactivity is reversibly reduced after Mn-treatment. This led us to propose that reduced dopamine neuromodulation could drive the changes in startle movements. To test this, when we supplemented dopamine to Mn-treated larvae, the larvae exhibited normal number of startle swims. Taken together, these results indicate that Mn interferes with neuronal function at the sensory, motor, and modulatory levels, and open avenues for therapeutically targeted studies on the zebrafish model of manganism.
Author Thirumalai, Vatsala
Das Sharma, Shreya
Bakthavatsalam, Subha
Sonawane, Mahendra
Datta, Ankona
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  surname: Datta
  fullname: Datta, Ankona
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Snippet Abstract Manganese (Mn) is essential for neuronal function, yet toxic at high concentrations. Environmental and occupational exposure to high concentrations of...
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Title A zebrafish model of manganism reveals reversible and treatable symptoms independent of neurotoxicity
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