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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.

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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

Authors
  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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