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Activated p38 MAPK is associated with decreased CSF 5-HIAA and increased maternal rejection during infancy in rhesus monkeys

Molecular Psychiatry volume 12, pages 895–897 (2007)Cite this article

Recent data indicate that activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade by cytokines including interleukin (IL)-1 and tumor necrosis factor (TNF)-α increases the expression and activity of the serotonin transporter (SERT). Herein, we report that increased p38 activity, as manifested by an increased percentage of peripheral blood monocytes staining positive for intracellular phosphorylated p38 (p-p38), was associated with decreased cerebrospinal fluid (CSF) concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and increased maternal rejection in 17 rhesus monkeys, 8 of whom were exposed to poor maternal care as infants. These data provide the first evidence of an in vivo relationship between p38 MAPK activation and brain serotonin metabolism in an animal model of early life stress and indicate that activation of p38 MAPK signaling pathways may participate in the contribution of early life stress to psychiatric morbidity.

Early life stress including physical/sexual abuse as well as neglect has been associated with a number of adverse health outcomes including increased anxiety and depression.1 We recently reported that adolescent rhesus monkeys (Macaca mulatta) exposed to physical abuse and high levels of maternal rejection as infants exhibit increased distress and anxiety, delayed social development and reduced exploration, compared to non-abused animals.2, 3 This early exposure to poor maternal care was also associated with reduced brain serotonergic function as reflected by decreased CSF concentrations of serotonin (5-HT) and the serotonin metabolite, 5-HIAA, that were in turn correlated with increased anxiety-like behavior during adolescence.4

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References

  1. Heim C, Nemeroff CB . Biol Psychiatry 2001; 49: 1023–1039.

    Article  CAS  Google Scholar 

  2. McCormack K, Sanchez MM, Bardi M, Maestripieri D . Dev Psychobiol 2006; 48: 537–550.

    Article  CAS  Google Scholar 

  3. Sanchez MM . Horm Behav 2006; 50: 623–631.

    Article  Google Scholar 

  4. Maestripieri D, McCormack KM, Higley JD, Lindell SG, Sanchez MM . Behav Brain Res 2006; 175: 90–95.

    Article  CAS  Google Scholar 

  5. Pace TWW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH et al. Am J Psychiatry 2006; 163: 1630–1633.

    Article  Google Scholar 

  6. Raison CL, Capuron C, Miller AH . Trends Immunol 2006; 227: 24–31.

    Article  Google Scholar 

  7. Zhu CB, Carneriro AM, Dostmann WR, Hewlett WA, Blakely RD . J Biol Chem 2005; 280: 15649–15658.

    Article  CAS  Google Scholar 

  8. Maestripieri D, Lindell SG, Higley JD, Newman TK, McCormack KM, Sanchez MM . Behav Neurosci 2006; 120: 1017–1024.

    Article  Google Scholar 

  9. Higley JD, Suomi SJ, Linnoila M . Alcohol clin Exp Res 1996; 20: 643–650.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by NIH Grants MH65046 (MMS), MH62577 (DM), MH069124 and MH020018 (AHM) and RR-00165 (Yerkes National Primate Res Ctr).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, USA

    M M Sanchez, O Alagbe, J C Felger, J Zhang & A H Miller

  2. Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA

    M M Sanchez, A E Graff, A P Grand & D Maestripieri

  3. Department of Psychology, University of Georgia, Athens, GA, USA

    A P Grand

  4. Department of Comparative Human Development, University of Chicago, Chicago, IL, USA

    D Maestripieri

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  1. M M Sanchez
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  2. O Alagbe
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  3. J C Felger
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  4. J Zhang
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  5. A E Graff
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  6. A P Grand
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  7. D Maestripieri
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  8. A H Miller
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Correspondence to A H Miller.

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Sanchez, M., Alagbe, O., Felger, J. et al. Activated p38 MAPK is associated with decreased CSF 5-HIAA and increased maternal rejection during infancy in rhesus monkeys. Mol Psychiatry 12, 895–897 (2007). https://doi.org/10.1038/sj.mp.4002025

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