PUBLICATION
A Zebrafish model of human manganism points to specific deficits in sensory, motor, and neuro-modulatory functions
- Authors
- Bakthavatsalam, S., Das Sharma, S., Sonawane, M., Thirumalai, V., Datta, A.
- ID
- ZDB-PUB-140928-2
- Date
- 2014
- Source
- Disease models & mechanisms 7(11): 1239-51 (Journal)
- Registered Authors
- Sonawane, Mahendra
- Keywords
- none
- MeSH Terms
-
- Animals
- Manganese/toxicity*
- Nervous System/drug effects*
- Nervous System/enzymology
- Tyrosine 3-Monooxygenase/metabolism
- Zebrafish
- PubMed
- 25261567 Full text @ Dis. Model. Mech.
Citation
Bakthavatsalam, S., Das Sharma, S., Sonawane, M., Thirumalai, V., Datta, A. (2014) A Zebrafish model of human manganism points to specific deficits in sensory, motor, and neuro-modulatory functions. Disease models & mechanisms. 7(11):1239-51.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping