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A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.
PLoS One. 2011; 6(9):e24840.Plos

Abstract

The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5-/- mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies.

Authors+Show Affiliations

Department of Molecular Medicine, Byrd Alzheimer's Research Institute, University of South Florida, Tampa, Florida, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21935478

Citation

O'Leary, John C., et al. "A New Anti-depressive Strategy for the Elderly: Ablation of FKBP5/FKBP51." PloS One, vol. 6, no. 9, 2011, pp. e24840.
O'Leary JC, Dharia S, Blair LJ, et al. A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51. PLoS One. 2011;6(9):e24840.
O'Leary, J. C., Dharia, S., Blair, L. J., Brady, S., Johnson, A. G., Peters, M., Cheung-Flynn, J., Cox, M. B., de Erausquin, G., Weeber, E. J., Jinwal, U. K., & Dickey, C. A. (2011). A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51. PloS One, 6(9), e24840. https://doi.org/10.1371/journal.pone.0024840
O'Leary JC, et al. A New Anti-depressive Strategy for the Elderly: Ablation of FKBP5/FKBP51. PLoS One. 2011;6(9):e24840. PubMed PMID: 21935478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51. AU - O'Leary,John C,3rd AU - Dharia,Sheetal, AU - Blair,Laura J, AU - Brady,Sarah, AU - Johnson,Amelia G, AU - Peters,Melinda, AU - Cheung-Flynn,Joyce, AU - Cox,Marc B, AU - de Erausquin,Gabriel, AU - Weeber,Edwin J, AU - Jinwal,Umesh K, AU - Dickey,Chad A, Y1 - 2011/09/15/ PY - 2011/07/06/received PY - 2011/08/22/accepted PY - 2011/9/22/entrez PY - 2011/9/22/pubmed PY - 2012/3/1/medline SP - e24840 EP - e24840 JF - PloS one JO - PLoS One VL - 6 IS - 9 N2 - The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5-/- mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21935478/A_new_anti_depressive_strategy_for_the_elderly:_ablation_of_FKBP5/FKBP51_ L2 - https://dx.plos.org/10.1371/journal.pone.0024840 DB - PRIME DP - Unbound Medicine ER -