Electroconvulsive seizure-induced changes in gene expression in the mouse hypothalamic paraventricular nucleus

J Psychopharmacol. 2013 Nov;27(11):1058-69. doi: 10.1177/0269881113497612. Epub 2013 Jul 17.

Abstract

Electroconvulsive therapy is an effective and rapid treatment for depression. In patients with depression, the function of the paraventricular nucleus of the hypothalamus (PVN) is frequently altered. Electroconvulsive seizure (ECS), which is a model of electroconvulsive therapy, upregulates the expression of c-fos in the PVN of animal models. Therefore, we hypothesized that ECS alters gene expression and function in the PVN. The PVN was microdissected from mouse brain sections following ECS treatment, and total RNA was analyzed by microarray. Two hours after ECS, the levels of expression of 2.6% (589 genes) of the genes showed a greater than 2-fold decrease and 0.9% (205 genes) showed a greater than 2-fold increase. Among these genes, 72 of the downregulated genes and 12 of the upregulated genes have been proposed to be associated with psychiatric disorders, such as depression, by knowledge database analyses. The groups of downregulated genes included neuropeptides (Cck), kinases (Prkcb, Camk2a), transcription factors (Tcf4), and transporters (Aqp4), and these have been suggested to be associated with psychiatric disorders and/or PVN function. The results of the present study indicated that ECS treatment could modulate PVN functions through altered gene expression, which may contribute to its antidepressant effects.

Keywords: Antidepressant treatment; electroconvulsive seizure; microarray; microdissection; paraventricular hypothalamus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electroshock*
  • Gene Expression Regulation*
  • Male
  • Mice
  • Nucleic Acid Amplification Techniques
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA / biosynthesis
  • RNA / genetics
  • Seizures / genetics*
  • Seizures / metabolism
  • Transcriptome / genetics*

Substances

  • Proto-Oncogene Proteins c-fos
  • RNA