Cocaine modulates the expression of transcription factors related to the dopaminergic system in zebrafish
- Authors
- Katherine, B.V., Roger, L.B., and Rodríguez, R.E.
- ID
- ZDB-PUB-121212-11
- Date
- 2013
- Source
- Neuroscience 231: 258-271 (Journal)
- Registered Authors
- Keywords
- transcription factors, dopamine system, cocaine, zebrafish, embryogenesis
- MeSH Terms
-
- Animals
- Cocaine/pharmacology*
- Dopamine Plasma Membrane Transport Proteins/genetics
- Dopamine Plasma Membrane Transport Proteins/metabolism*
- Dopamine Uptake Inhibitors/pharmacology*
- Gene Expression/drug effects*
- Gene Expression Regulation, Developmental/drug effects*
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Neurons/drug effects
- Neurons/metabolism
- Nuclear Receptor Subfamily 4, Group A, Member 2/genetics
- Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Tyrosine 3-Monooxygenase/genetics
- Tyrosine 3-Monooxygenase/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 23219907 Full text @ Neuroscience
Nodal-related protein, Ndr2, and transcription factors such as Lmx1b, Otp, Nurr1 and Pitx3 are very important in the differentiation, function and maintenance of mesodiencephalic dopaminergic neurons, and are necessary for the activation of tyrosine hydroxylase and dopamine transporter expression. Hence, the aim of the present work was to evaluate the effects of cocaine on the expression of genes related to the embryogenesis development of the dopaminergic system. Zebrafish embryos were exposed to cocaine hydrochloride at 5 hours post-fertilization (hpf), and collected at two important stages -24 and 48 hpf- to study the effects of cocaine on the expression of ndr2, the lmx1b.1, lmx1b.2, otpa, otpb, nurr1 transcription factors, and their target genes: tyrosine hydroxylase and dopamine transporter expression. Our results by qPCR showed that cocaine affects the expression of these genes in different ways, depending on the stage of development. Furthermore by in situ hybridization we observed a change in the spatial distribution of lmx1b.1 and lmx1b.2 at both stages, (24 and 48 hpf) due to exposure to cocaine. We also show the importance of Lmx1b and Otp in th expression through the knockdown of Lmx1b.1 and Lmx1b.2, and of Otpa and Otpb. Additionally, cocaine produced an increase and a decrease in tyrosine hydroxylase levels at 24 hpf and at 48 hpf, respectively, possibly due to the change in the expression of the transcription factors and ndr2 expression. We conclude that cocaine alters the correct development of dopaminergic system affecting the expression of transcription factors, during the embryogenesis.