Selective toxicity of L-DOPA to dopamine transporter-expressing neurons and locomotor behavior in zebrafish larvae

Sarah J Stednitz; Briana Freshner; Samantha Shelton; Tori Shen; Donovan Black; Ethan Gahtan

doi:10.1016/j.ntt.2015.11.001

Selective toxicity of L-DOPA to dopamine transporter-expressing neurons and locomotor behavior in zebrafish larvae

Neurotoxicol Teratol. 2015 Nov-Dec;52(Pt A):51-6. doi: 10.1016/j.ntt.2015.11.001. Epub 2015 Nov 3.

Authors

Sarah J Stednitz¹, Briana Freshner², Samantha Shelton³, Tori Shen⁴, Donovan Black², Ethan Gahtan⁵

Affiliations

¹ Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of Oregon, Eugene, Institute of Neuroscience, United States.
² Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States.
³ Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of Massachusetts, Boston, Department of Neuroscience, United States.
⁴ Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of California, San Diego, Eating Disorders Center for Treatment & Research, United States.
⁵ Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States. Electronic address: ethan.gahtan@humboldt.edu.

PMID: 26546233
DOI: 10.1016/j.ntt.2015.11.001

Abstract

Dopamine signaling is conserved across all animal species and has been implicated in the disease process of many neurological disorders, including Parkinson's disease (PD). The primary neuropathology in PD involves the death of dopaminergic cells in the substantia nigra (SN), an anatomical region of the brain implicated in dopamine production and voluntary motor control. Increasing evidence suggests that the neurotransmitter dopamine may have a neurotoxic metabolic product (DOPAL) that selectively damages dopaminergic cells. This study was designed to test this theory of oxidative damage in an animal model of Parkinson's disease, using a transgenic strain of zebrafish with fluorescent labeling of cells that express the dopamine transporter. The pretectum and ventral diencephalon exhibited reductions in cell numbers due to L-DOPA treatment while reticulospinal neurons that do not express the DAT were unaffected, and this was partially rescued by monoamine oxidase inhibition. Consistent with the MPTP model of PD in zebrafish larvae, spontaneous locomotor behavior in L-DOPA treated animals was depressed following a 24-h recovery period, while visually-evoked startle response rates and latencies were unaffected.

Keywords: Dopamine transporter; L-DOPA; Monoamine oxidase; Neurotoxicity; Parkinson's; Zebrafish.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Diencephalon / drug effects
Diencephalon / metabolism
Disease Models, Animal
Dopamine Plasma Membrane Transport Proteins / metabolism*
Dopaminergic Neurons / drug effects*
Dopaminergic Neurons / metabolism*
Levodopa / toxicity*
Motor Activity / drug effects*
Oxidative Stress / drug effects
Pretectal Region / drug effects
Pretectal Region / metabolism
Zebrafish

Substances

Dopamine Plasma Membrane Transport Proteins
Levodopa