The role of neuronal nitric oxide and its pathways in the protection and recovery from neurotoxin-induced <em>de novo</em> hypokinetic motor behaviors in the embryonic zebrafish (<em>Danio rerio</em>)

Amber Woodard; Brandon Barbery; Reid Wilkinson; Jonathan Strozyk; Mathew Milner; Patrick Doucette; Jarred Doran; Kendra Appleby; Henry Atwill; Wade E. Bell; James E. Turner; Amber Woodard; Brandon Barbery; Reid Wilkinson; Jonathan Strozyk; Mathew Milner; Patrick Doucette; Jarred Doran; Kendra Appleby; Henry Atwill; Wade E. Bell; James E. Turner

doi:10.3934/Neuroscience.2019.1.25

AIMS Neuroscience

2019, Volume 6, Issue 1: 25-42. doi: 10.3934/Neuroscience.2019.1.25

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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)

Department of Biology, Center for Molecular, Cellular, and Biological Chemistry, Virginia Military Institute, Lexington, VA 24450, USA

Received: 03 October 2018 Accepted: 13 February 2019 Published: 28 March 2019

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.
- neuronal nitric oxide synthase (nNOS),
- nNOS inhibitor,
- DTT,
- ODQ,
- motor dysfunction,
- dopamine,
- 6-hydroxydopamine neuronal toxicity,
- zebrafish
Citation: Amber Woodard, Brandon Barbery, Reid Wilkinson, Jonathan Strozyk, Mathew Milner, Patrick Doucette, Jarred Doran, Kendra Appleby, Henry Atwill, Wade E. Bell, James E. Turner. 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)[J]. AIMS Neuroscience, 2019, 6(1): 25-42. doi: 10.3934/Neuroscience.2019.1.25

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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.

Abbreviation nNOS: neuronal nitric oxide synthase;
Acknowledgments

This research was supported from grant funding from the Reid '41 Institute Professorship in the Arts and Sciences (awarded to JET), the VMI Department of Biology, the VMI Center for Undergraduate Research.

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