Expression profile of neurotransmitter receptor and regulatory genes in the prefrontal cortex of spontaneously hypertensive rats: relevance to neuropsychiatric disorders

Psychiatry Res. 2014 Nov 30;219(3):674-9. doi: 10.1016/j.psychres.2014.05.034. Epub 2014 Jun 5.

Abstract

The spontaneously hypertensive rat (SHR) strain was shown to be a useful animal model to study several behavioral, pathophysiological and pharmacological aspects of schizophrenia and attention-deficit/hyperactivity disorder. To further understand the genetic underpinnings of this model, our primary goal in this study was to compare the gene expression profile of neurotransmitter receptors and regulators in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of SHR and Wistar rats (control group). In addition, we investigated DNA methylation pattern of promoter region of the genes differentially expressed. We performed gene expression analysis using a PCRarray technology, which simultaneously measures the expression of 84 genes related to neurotransmission. Four genes were significantly downregulated in the PFC of SHR compared to Wistar rats (Gad2, Chrnb4, Slc5a7, and Qrfpr) and none in nucleus accumbens. Gad2 and Qrfpr have CpG islands in their promoter region. For both, the promoter region was hypomethylated in SHR group, and probably this mechanism is not related with the downregulation of these genes. In summary, we identified genes that are downregulated in the PFC of SHR, and might be related to the behavioral abnormalities exhibited by this strain.

Keywords: Chrnb4; DNA methylation; Gad2; Gene expression; Qrfpr; Slc5a7; Spontaneously hypertensive rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Attention Deficit Disorder with Hyperactivity / psychology*
  • CpG Islands
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Gene Expression
  • Glutamate Decarboxylase
  • Male
  • Nerve Tissue Proteins
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiopathology
  • Polymerase Chain Reaction
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Rats, Wistar
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter / genetics*
  • Receptors, Nicotinic
  • Symporters
  • Synaptic Transmission*

Substances

  • Chrnb4 protein, mouse
  • Nerve Tissue Proteins
  • Qrfpr protein, rat
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter
  • Receptors, Nicotinic
  • SLC5A7 protein, human
  • Symporters
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2