Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein

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• 作者：Amalia Tsolakidou (1) (3)
  Ludwig Czibere (1)
  Benno Pütz (1)
  Dietrich Trümbach (2) (2)
  Markus Panhuysen (1)
  Jan M Deussing (1)
  Wolfgang Wurst (1) (2) (2)
  Inge Sillaber (1)
  Rainer Landgraf (1)
  Florian Holsboer (1)
  Theo Rein (1)
  
• 刊名：BMC Genomics
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：11
• 期：1
• 全文大小：674KB
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• 作者单位：Amalia Tsolakidou (1) (3)
  Ludwig Czibere (1)
  Benno Pütz (1)
  Dietrich Trümbach (2) (2)
  Markus Panhuysen (1)
  Jan M Deussing (1)
  Wolfgang Wurst (1) (2) (2)
  Inge Sillaber (1)
  Rainer Landgraf (1)
  Florian Holsboer (1)
  Theo Rein (1)
  
  1. Max-Planck Institute of Psychiatry, Munich, Germany
  3. Department of Psychiatry and Psychotherapy, Technical University of Munich, Munich, Germany
  2. Helmholtz Centre and Technical University Munich, Institute for Developmental Genetics, Neuherberg, Germany
  2. German Centre for Neurodegenerative Diseases, Munich, Germany
  

文摘

Background The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure. Gene expression and regulation was determined by microarray analyses and further evaluated by bioinformatics tools including pathway and cluster analyses. Results Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN), 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains. Our search for connections between the regulated genes resulted in potential novel signalling pathways in stress. In particular, Guanine nucleotide binding protein, alpha inhibiting 2 (GNAi2) and Amyloid β (A4) precursor protein (APP) were detected as stress-regulated genes, and together with other genes, seem to be integrated into stress-responsive pathways and gene networks in the PVN. Conclusions This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP) and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain.