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Article

Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus

by
Marangelie Criado-Marrero
,
Niat T. Gebru
,
Lauren A. Gould
,
Taylor M. Smith
,
Sojeong Kim
,
Roy J. Blackburn
,
Chad A. Dickey
† and
Laura J. Blair
*
Department of Molecular Medicine, USF Health Byrd Institute, University of South Florida, Tampa, FL 33613, USA
*
Author to whom correspondence should be addressed.
†
Deceased.
Int. J. Mol. Sci. 2019, 20(11), 2738; https://doi.org/10.3390/ijms20112738
Submission received: 17 April 2019 / Revised: 18 May 2019 / Accepted: 31 May 2019 / Published: 4 June 2019
(This article belongs to the Section Molecular Neurobiology)
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Abstract

Clinical studies show a significant association of childhood adversities and FK506-binding protein 5 (FKBP5) polymorphisms on increasing the susceptibility for neuropsychiatric disorders. However, the mechanisms by which early life stress (ELS) influences FKBP5 actions have not been fully elucidated. We hypothesized that interactions between ELS and high FKBP5 induce phenotypic changes that correspond to underlying molecular changes in the brain. To test this, we exposed newborn mice overexpressing human FKBP5 in the forebrain, rTgFKBP5, to ELS using a maternal separation. Two months after ELS, we observed that ELS increased anxiety levels, specifically in mice overexpressing FKBP5, an effect that was more pronounced in females. Biochemically, Protein kinase B (AKT) phosphorylation was reduced in the dorsal hippocampus in rTgFKBP5 mice, which demonstrates that significant molecular changes occur as a result of ELS when FKBP5 levels are altered. Taken together, our results have a significant impact on our understanding mechanisms underlying the gene x environment interaction showing that anxiety and AKT signaling in the hippocampus were affected by the combination of ELS and FKBP5. An increased knowledge of the molecular mechanisms underlying these interactions may help determine if FKBP5 could be an effective target for the treatment of anxiety and other mood-related illnesses.
Keywords: FKBP5; early life stress; anxiety; hippocampus; AKT FKBP5; early life stress; anxiety; hippocampus; AKT

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MDPI and ACS Style

Criado-Marrero, M.; Gebru, N.T.; Gould, L.A.; Smith, T.M.; Kim, S.; Blackburn, R.J.; Dickey, C.A.; Blair, L.J. Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. Int. J. Mol. Sci. 2019, 20, 2738. https://doi.org/10.3390/ijms20112738

AMA Style

Criado-Marrero M, Gebru NT, Gould LA, Smith TM, Kim S, Blackburn RJ, Dickey CA, Blair LJ. Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. International Journal of Molecular Sciences. 2019; 20(11):2738. https://doi.org/10.3390/ijms20112738

Chicago/Turabian Style

Criado-Marrero, Marangelie, Niat T. Gebru, Lauren A. Gould, Taylor M. Smith, Sojeong Kim, Roy J. Blackburn, Chad A. Dickey, and Laura J. Blair. 2019. "Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus" International Journal of Molecular Sciences 20, no. 11: 2738. https://doi.org/10.3390/ijms20112738

APA Style

Criado-Marrero, M., Gebru, N. T., Gould, L. A., Smith, T. M., Kim, S., Blackburn, R. J., Dickey, C. A., & Blair, L. J. (2019). Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. International Journal of Molecular Sciences, 20(11), 2738. https://doi.org/10.3390/ijms20112738

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