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

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.

• Authors: Sarah J Stednitz, Briana Freshner, Samantha Shelton, Tori Shen, Donovan Black, Ethan Gahtan
• Journal: Neurotoxicology and teratology (Neurotoxicol Teratol) 2015 Nov-Dec Vol. 52 Issue Pt A Pg. 51-6 ISSN: 1872-9738 [Electronic] United States
• PMID: 26546233 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Levodopa

Topics

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