PUBLICATION
The role of neuronal nitric oxide and its pathways in the protection and recovery from neurotoxin-induced de novo hypokinetic motor behaviors in the embryonic zebrafish (Danio rerio)
- Authors
- Woodard, A., Barbery, B., Wilkinson, R., Strozyk, J., Milner, M., Doucette, P., Doran, J., Appleby, K., Atwill, H., Bell, W.E., Turner, J.E.
- ID
- ZDB-PUB-200429-9
- Date
- 2019
- Source
- AIMS neuroscience 6: 25-42 (Journal)
- Registered Authors
- Keywords
- 6-hydroxydopamine neuronal toxicity, DTT, ODQ, dopamine, motor dysfunction, nNOS inhibitor, neuronal nitric oxide synthase (nNOS), zebrafish
- MeSH Terms
- none
- PubMed
- 32341966 Full text @ AIMS Neurosci
Citation
Woodard, A., Barbery, B., Wilkinson, R., Strozyk, J., Milner, M., Doucette, P., Doran, J., Appleby, K., Atwill, H., Bell, W.E., Turner, J.E. (2019) The role of neuronal nitric oxide and its pathways in the protection and recovery from neurotoxin-induced de novo hypokinetic motor behaviors in the embryonic zebrafish (Danio rerio). AIMS neuroscience. 6:25-42.
Abstract
Neuronal nitric oxide (nNO) has been shown to affect motor function in the brain. Specifically, nNO acts in part through regulation of dopamine (DA) release, transporter function, and the elicitation of neuroprotection/neurodegeneration of neurons in conditions such as Parkinson's disease (PD). Recently, the zebrafish has been proposed to be a new model for the study of PD since neurotoxin damage to their nigrostriatal-like neurons exhibit PD-like motor dysfunctions similar to those of mammalian models and human patients. Results from this study demonstrate that treatment of 5 days post fertilization (dpf) fish with a nNO synthase inhibitor as a co-treatment with 6-OHDA facilitates long-term survival and accelerates the recovery from 6-OHDA-induced hypokinesia-like symptoms. These findings are unique in that under conditions of neurotoxin-induced stress, the inhibition of the NO-related S-nitrosylation indirect pathway dramatically facilitates recovery from 6-OHDA treatment but inhibition of the NO-sGC-cGMP direct pathway is essential for survival in 5 dpf treated fish. In conclusion, these results indicate that nNOS and the inhibition of the NO-linked S-nitrosylation pathway plays an important role in antagonizing the protection and recovery of fish from neurotoxin treatment. These data begin to help in the understanding of the role of NO as a neuroprotectant in dopaminergic pathways, particularly those that influence motor dysfunctions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping