The brain-specific Neural Zinc Finger transcription factor 2b (NZF-2b/7ZFMyt1) causes suppression of cocaine-induced locomotor activity.
- Chandrasekar V Division of Biochemistry, Department of Medicine, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland.
- Dreyer JL
- 2009-09-30
Published in:
- Neurobiology of disease. - 2010
Animals
Brain
Brain-Derived Neurotrophic Factor
Cocaine
Dopamine Uptake Inhibitors
Gene Knockdown Techniques
Gene Transfer Techniques
Genetic Vectors
Inverted Repeat Sequences
Lentivirus
Locomotion
Male
Nerve Tissue Proteins
Neurons
Nucleus Accumbens
RNA
RNA, Messenger
Rats
Rats, Wistar
Repressor Proteins
Transcription Factors
English
Chronic cocaine induces high expression of the brain-specific Neural-Zinc-Finger transcription factor-2b (NZF-2b/7ZFMyt1), particularly in the mesolimbic dopaminergic pathway, resulting in a 11-fold increase in NZF-2b/7ZFMyt1 expression in the Nucleus Accumbens (NAc). Overexpression of this gene in the NAc with a NZF-2b/7ZFMyt1-expressing lentivirus resulted in >55% decrease in locomotor activity upon chronic cocaine administration, compared to control animals. In contrast knocking-down the gene in the NAc with lentiviruses expressing shRNAs against NZF-2b/7ZFMyt1 induced strong hyperlocomotor activity upon cocaine. Strong inhibition of BDNF is observed upon NZF-2b/7ZFMyt1 expression, concomitant with strong induction of transcription factors REST1 (RE silencing transcription factor-1) and NAC1, probably leading to regulation of gene expression by interaction with histone deacetylases. These changes lead to decreased responsiveness of the animal to the locomotor-activating effects of cocaine, indicating that NZF-2b/7ZFMyt1 expression plays an important role in phenotypic changes induced by the drug.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.nbd.2009.09.010
- PMID 19786102
- Persistent URL
- https://sonar.ch/global/documents/98337
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