Evidence Revealing Deregulation of the KLF11-Mao A Pathway in Association with Chronic Stress and Depressive Disorders

Sharonda Harris, Shakevia Johnson, Jeremy W. Duncan, Chinelo Udemgba, Jeffrey H. Meyer, Paul R. Albert, Gwen Lomberk, Raul Urrutia, Xiao Ming Ou, Craig A. Stockmeier, Jun Ming Wang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The biochemical pathways underlying major depressive disorder (MDD) and chronic stress are not well understood. However, it has been reported that monoamine oxidase A (MAO A, a major neurotransmitter-degrading enzyme) is significantly increased in the brains of human subjects affected with MDD and rats exposed to chronic social defeat (CSD) stress, which is used to model depression. In the current study, we compared the protein levels of a MAO A-transcriptional activator, Kruppel-like factor 11 (KLF11, also recognized as transforming growth factor-beta-inducible early gene 2) between the brains of 18 human subjects with MDD and 18 control subjects. We found that, indeed, the expression of KLF11 is increased by 36% (p<0.02) in the postmortem prefrontal cortex of human subjects with MDD compared with controls. We also observed a positive correlation between KLF11 levels and those of its target gene, MAO A, both in association with MDD. KLF11 protein expression was also increased by 44% (p<0.02) in the frontal cortex of KLF11 wild-type mice (Klf11 <sup>+/+</sup>) vs Klf11 <sup>-/-</sup> when both exposed to CSD stress. In contrast, locomotor activities, central box duration and sucrose preference were significantly reduced in the stressed Klf11 <sup>+/+</sup> mice, suggesting that Klf11 <sup>+/+</sup> mice are more severely affected by the stress model compared with Klf11 <sup>-/-</sup> mice. These results serve to assign an important role of KLF11 in upregulating MAO A in MDD and chronic social stress, suggesting that inhibition of the pathways regulated by this transcription factor may aid in the therapeutics of neuropsychiatric illnesses. Thus, the new knowledge derived from the current study extends our understanding of transcriptional mechanisms that are operational in the pathophysiology of common human diseases and thus bears significant biomedical relevance.

Original languageEnglish (US)
Pages (from-to)1373-1382
Number of pages10
JournalNeuropsychopharmacology
Volume40
Issue number6
DOIs
StatePublished - May 1 2015

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Monoamine Oxidase
Major Depressive Disorder
Depressive Disorder
Kruppel-Like Transcription Factors
Brain
Locomotion
Transforming Growth Factor beta
Neurotransmitter Agents
Sucrose
Transcription Factors
Depression
Enzymes
Genes
Proteins
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Harris, S., Johnson, S., Duncan, J. W., Udemgba, C., Meyer, J. H., Albert, P. R., ... Wang, J. M. (2015). Evidence Revealing Deregulation of the KLF11-Mao A Pathway in Association with Chronic Stress and Depressive Disorders. Neuropsychopharmacology, 40(6), 1373-1382. https://doi.org/10.1038/npp.2014.321

Evidence Revealing Deregulation of the KLF11-Mao A Pathway in Association with Chronic Stress and Depressive Disorders. / Harris, Sharonda; Johnson, Shakevia; Duncan, Jeremy W.; Udemgba, Chinelo; Meyer, Jeffrey H.; Albert, Paul R.; Lomberk, Gwen; Urrutia, Raul; Ou, Xiao Ming; Stockmeier, Craig A.; Wang, Jun Ming.

In: Neuropsychopharmacology, Vol. 40, No. 6, 01.05.2015, p. 1373-1382.

Research output: Contribution to journalArticle

Harris, S, Johnson, S, Duncan, JW, Udemgba, C, Meyer, JH, Albert, PR, Lomberk, G, Urrutia, R, Ou, XM, Stockmeier, CA & Wang, JM 2015, 'Evidence Revealing Deregulation of the KLF11-Mao A Pathway in Association with Chronic Stress and Depressive Disorders', Neuropsychopharmacology, vol. 40, no. 6, pp. 1373-1382. https://doi.org/10.1038/npp.2014.321
Harris, Sharonda ; Johnson, Shakevia ; Duncan, Jeremy W. ; Udemgba, Chinelo ; Meyer, Jeffrey H. ; Albert, Paul R. ; Lomberk, Gwen ; Urrutia, Raul ; Ou, Xiao Ming ; Stockmeier, Craig A. ; Wang, Jun Ming. / Evidence Revealing Deregulation of the KLF11-Mao A Pathway in Association with Chronic Stress and Depressive Disorders. In: Neuropsychopharmacology. 2015 ; Vol. 40, No. 6. pp. 1373-1382.
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