Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior

R. J. Oliver, J. L. Brigman, F. Bolognani, A. M. Allan, Janet Neisewander, N. I. Perrone-Bizzozero

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The neuronal RNA-binding protein HuD is involved in synaptic plasticity and learning and memory mechanisms. These effects are thought to be due to HuD-mediated stabilization and translation of target mRNAs associated with plasticity. To investigate the potential role of HuD in drug addiction, we first used bioinformatics prediction algorithms together with microarray analyses to search for specific genes and functional networks upregulated within the forebrain of HuD overexpressing mice (HuDOE). When this set was further limited to genes in the knowledgebase of addiction-related genes database (KARG) that contains predicted HuD-binding sites in their 3′ untranslated regions (3′UTRs), we found that HuD regulates networks that have been associated with addiction-like behavior. These genes included Bdnf and Camk2a, 2 previously validated HuD targets. Since addiction is hypothesized to be a disorder stemming from altered gene expression causing aberrant plasticity, we sought to test the role of HuD in cocaine conditioned placed preference (CPP), a model of addiction-related behaviors. HuD mRNA and protein were upregulated by CPP within the nucleus accumbens of wild-type C57BL/6J mice. These changes were associated with increased expression of Bdnf and Camk2a mRNA and protein. To test this further, we trained HuDOE and wild-type mice in CPP and found that HuDOE mice showed increased cocaine CPP compared with controls. This was also associated with elevated expression of HuD target mRNAs and proteins, CaMKIIα and BDNF. These findings suggest HuD involvement in addiction-related behaviors such as cocaine conditioning and seeking, through increased plasticity-related gene expression.

Original languageEnglish (US)
JournalGenes, Brain and Behavior
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

RNA-Binding Proteins
Gene Expression
Cocaine
Messenger RNA
Genes
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neuronal Plasticity
Knowledge Bases
Gene Regulatory Networks
Brain-Derived Neurotrophic Factor
Nucleus Accumbens
Protein Biosynthesis
3' Untranslated Regions
Microarray Analysis
Prosencephalon
Computational Biology
Inbred C57BL Mouse
Substance-Related Disorders
Proteins
Binding Sites

Keywords

  • BDNF
  • CaMKIIα
  • CPP
  • HuD
  • Nucleus accumbens
  • Post-transcriptional regulation
  • RNA-binding protein

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Oliver, R. J., Brigman, J. L., Bolognani, F., Allan, A. M., Neisewander, J., & Perrone-Bizzozero, N. I. (Accepted/In press). Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior. Genes, Brain and Behavior. https://doi.org/10.1111/gbb.12454

Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior. / Oliver, R. J.; Brigman, J. L.; Bolognani, F.; Allan, A. M.; Neisewander, Janet; Perrone-Bizzozero, N. I.

In: Genes, Brain and Behavior, 01.01.2018.

Research output: Contribution to journalArticle

Oliver, R. J. ; Brigman, J. L. ; Bolognani, F. ; Allan, A. M. ; Neisewander, Janet ; Perrone-Bizzozero, N. I. / Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior. In: Genes, Brain and Behavior. 2018.
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