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Amygdala protein kinase C epsilon regulates corticotropin-releasing factor and anxiety-like behavior

H M B Lesscher1, T McMahon, A W Lasek

  • 1Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.

Genes, Brain, and Behavior
|October 3, 2007
PubMed

Insights

Protein kinase C epsilon (PKCepsilon) regulates anxiety-like behavior by controlling corticotropin-releasing factor (CRF) in the amygdala. PKCepsilon deficiency reduces anxiety and CRF levels, suggesting a novel therapeutic target for affective disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Corticotropin-releasing factor (CRF) and its signaling pathways are key targets for treating affective disorders.
  • The role of protein kinase C epsilon (PKCepsilon) in regulating CRF expression and anxiety-like behavior is not well understood.

Purpose of the Study:

  • To investigate the role of PKCepsilon in the amygdala in the regulation of CRF and anxiety-like behavior.
  • To determine if PKCepsilon modulates CRF expression and influences anxiety-like behaviors.

Main Methods:

  • Utilized PKCepsilon null mutant mice and wild-type mice.
  • Employed RNA interference to reduce PKCepsilon levels in primary amygdala neurons and in vivo.
  • Administered selective PKCepsilon activator (psiepsilonRACK) and CRF.
  • Measured CRF messenger RNA and peptide levels.
  • Assessed anxiety-like behavior.

Main Results:

  • PKCepsilon null mutant mice exhibited reduced anxiety-like behavior and lower amygdala CRF levels.
  • PKCepsilon activation increased pro-CRF levels in amygdala neurons.
  • PKCepsilon knockdown blocked phorbol ester-induced CRF increases and reduced anxiety-like behavior in wild-type mice.
  • CRF infusion into the amygdala of PKCepsilon null mutant mice increased anxiety-like behavior.

Conclusions:

  • PKCepsilon plays a critical role in controlling anxiety-like behavior via the regulation of CRF in the amygdala.
  • This study reveals a novel mechanism linking PKCepsilon signaling to CRF expression and anxiety.
  • Targeting PKCepsilon may offer a new therapeutic strategy for affective disorders.

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