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Author Notes:

Corresponding Author: Phone: +1 334 844 4850; Fax: +1 334 844 9234, wootemc@auburn.edu (M.C.W.)

The authors have no competing financial interests.

Subjects:

Research Funding:

This work was supported by NIH-2RO1NS033661 (MCW). We thank Dr. Mike Irwin and Dr. Carl Pinkert at the Auburn University Transgenic Facility for their assistance in generation of the overexpression mice. We also thank Dr. Jorge Moscat and Dr. Maria-Theresa Diaz-Meco for their fruitful discussions and continued support.

Keywords:

  • Mitochondria
  • SQSTM1/p62
  • Animal models
  • Affective spectrum disorders
  • Depression
  • Anxiety

Behavioral Effects of SQSTM1/p62 Overexpression in Mice: Support for a Mitochondrial Role in Depression and Anxiety

Tools:

Journal Title:

Behavioural Brain Research

Volume:

Volume 248

Publisher:

, Pages 94-103

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Affective spectrum and anxiety disorders have come to be recognized as the most prevalently diagnosed psychiatric disorders. Among a suite of potential causes, changes in mitochondrial energy metabolism and function have been associated with such disorders. Thus, proteins that specifically change mitochondrial functionality could be identified as molecular targets for drugs related to treatment for affective spectrum disorders. Here, we report generation of transgenic mice overexpressing the scaffolding and mitophagy related protein Sequestosome1 (SQSTM1/p62) or a single point mutant (P392L) in the UBA domain of SQSTM1/p62. We show that overexpression of SQSTM1/p62 increases mitochondrial energy output and improves transcription factor import into the mitochondrial matrix. These elevated levels of mitochondrial functionality correlate directly with discernible improvements in mouse behaviors related to affective spectrum and anxiety disorders. We also describe how overexpression of SQSTM1/p62 improves spatial learning and long term memory formation in these transgenic mice. These results suggest that SQSTM1/p62 provides an attractive target for therapeutic agents potentially suitable for the treatment of anxiety and affective spectrum disorders.

Copyright information:

© 2013 Elsevier B.V. All rights reserved.

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