PUBLICATION
Cuprizone-induced dopaminergic hyperactivity and locomotor deficit in zebrafish larvae
- Authors
- Liu, M., Zheng, M., Zhang, W., Yang, F., Hong, L., Yu, X., Xu, H.
- ID
- ZDB-PUB-220128-6
- Date
- 2022
- Source
- Brain research 1780: 147802 (Journal)
- Registered Authors
- Zheng, Miaomiao
- Keywords
- cuprizone, dopaminergic hyp eractivity, locomotor activity, mitochondrial dysfunction, zebra fish larvae
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects
- Cuprizone/pharmacology*
- Disease Models, Animal
- Dopamine/metabolism*
- Dopaminergic Neurons/drug effects*
- Dopaminergic Neurons/metabolism
- Motor Activity/drug effects*
- Synaptic Transmission/drug effects*
- Zebrafish
- PubMed
- 35085574 Full text @ Brain Res.
Citation
Liu, M., Zheng, M., Zhang, W., Yang, F., Hong, L., Yu, X., Xu, H. (2022) Cuprizone-induced dopaminergic hyperactivity and locomotor deficit in zebrafish larvae. Brain research. 1780:147802.
Abstract
Cuprizone (CPZ) is a copper-chelator and toxic to mitochondria. Recent studies have shown oligodendrocyte (OL) loss and demyelination along with dopamine (DA) increase and behavioral abnormalities in CPZ-exposed mice, demonstrating its application in schizophrenia research. This study examined effects of CPZ exposure on autonomous behavior and dopaminergic neurotransmission in larval zebra fish. CPZ exposure was found to reduce the swimming velocity of zebra fish thus decreased swimming distance during day and night time. Moreover, the treatment induced a movement response of zebra fish larvae reacting to light-on/off switch featured by swimming velocity increase and decrease during the first and second half of the light-on/off phase, respectively. But, it abolished responses of zebra fish to sound-on/off seen in Control group. HPLC analysis showed elevated DA levels in the zebra fish, no change in NE and 5-HT levels. Transcriptome analysis reported changes in gene expression related to dopaminergic synapse and oxidative phosphorylation in CPZ-exposed larvae relative to Control group. Of the gene expression changes, up-regulation of drd2a, drd2b, drd4a and drd4rs was confirmed by RT-PCR, although no difference existed between Control and CPZ groups in dopaminergic neuron numbers. These results demonstrated dopaminergic hyperactivity and locomotor deficit in CPZ-exposed zebra fish larvae, encouraging further application of this model in exploring neurotoxic effects of CPZ on mitochondria and dopaminergic neurotransmission in zebra fish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping