PUBLICATION
Locomotor Behavior and Memory Dysfunction Induced by 3-Nitropropionic Acid in Adult Zebrafish: Modulation of Dopaminergic Signaling
- Authors
- Wiprich, M.T., da Rosa Vasques, R., Gusso, D., Rübensam, G., Kist, L.W., Bogo, M.R., Bonan, C.D.
- ID
- ZDB-PUB-230831-53
- Date
- 2023
- Source
- Molecular neurobiology 61(2): 609-621 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- 3-Nitropropionic acid, Dopaminergic system, Huntington’s disease, Locomotor dysfunction, Memory loss, Zebrafish
- MeSH Terms
-
- Animals
- Dopamine*/metabolism
- Dopamine Agonists/pharmacology
- Hypokinesia
- Memory Disorders/chemically induced
- Memory Disorders/drug therapy
- Neurodegenerative Diseases*
- Nitro Compounds*
- Propionates*
- Quinpirole/pharmacology
- Receptors, Dopamine D1/metabolism
- Receptors, Dopamine D2/metabolism
- Salicylamides*
- Zebrafish/metabolism
- PubMed
- 37648841 Full text @ Mol. Neurobiol.
Citation
Wiprich, M.T., da Rosa Vasques, R., Gusso, D., Rübensam, G., Kist, L.W., Bogo, M.R., Bonan, C.D. (2023) Locomotor Behavior and Memory Dysfunction Induced by 3-Nitropropionic Acid in Adult Zebrafish: Modulation of Dopaminergic Signaling. Molecular neurobiology. 61(2):609-621.
Abstract
Huntington's disease (HD) is a progressive neurodegenerative disease characterized by neuropsychiatric disturbance, cognitive impairment, and locomotor dysfunction. In the early stage (chorea) of HD, expression of dopamine D2 receptors (D2R) is reduced, whereas dopamine (DA) levels are increased. Contrary, in the late stage (bradykinesia), DA levels and the expression of D2R and dopamine D1 receptors (D1R) are reduced. 3-Nitropropionic acid (3-NPA) is a toxin that may replicate HD behavioral phenotypes and biochemical aspects. This study assessed the neurotransmitter levels, dopamine receptor gene expression, and the effect of acute exposure to quinpirole (D2R agonist) and eticlopride (D2R antagonist) in an HD model induced by 3-NPA in adult zebrafish. Quinpirole and eticlopride were acutely applied by i.p. injection in adult zebrafish after chronic treatment of 3-NPA (60 mg/kg). 3-NPA treatment caused a reduction in DA, glutamate, and serotonin levels. Quinpirole reversed the bradykinesia and memory loss induced by 3-NPA. Together, these data showed that 3-NPA acts on the dopaminergic system and causes biochemical alterations similar to late-stage HD. These data reinforce the hypothesis that DA levels are linked with locomotor and memory deficits. Thus, these findings may suggest that the use of DA agonists could be a pharmacological strategy to improve the bradykinesia and memory deficits in the late-stage HD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping