Histone Deacetylase 6 Gates the Synaptic Action of Acute Stress in Prefrontal Cortex

Overview

Journal J Physiol

Specialty Physiology

Date 2012 Feb 15

PMID 22331421

Citations 30

Authors

Janine B Lee

Jing Wei

Wenhua Liu

Jia Cheng

Jian Feng

Zhen Yan

Affiliations

Soon will be listed here.

Abstract

The prefrontal cortex (PFC), a region responsible for high-order cognitive functions, such as decision-making, attention and working memory, is highly influenced by stress and corticosteroid stress hormones. Recently it has been shown that acute stress affects PFC functions by potentiating glutamatergic transmission via a mechanism dependent on glucocorticoid receptor (GR) and its downstream target, serum and glucocorticoid-inducible kinase (SGK). To identify the key regulators of stress responses, we examined the role of histone deacetylase 6 (HDAC6), a unique member of the HDAC family that could regulate the GR chaperone protein heat shock protein 90 (HSP90), in the synaptic action of acute stress in PFC. We found that HDAC6 inhibition or knockdown blocked the enhancement of glutamatergic transmission and glutamate receptor trafficking by acute stress in vivo or corticosterone treatment in vitro. In addition, HDAC6 inhibition blocked the up-regulation of SGK in animals exposed to acute stress. HSP90 inhibition or knockdown produced a similar blockade of the acute stress-induced enhancement of glutamatergic signalling. These findings have identified HDAC6 as a key molecule gating the effects of acute stress on synaptic functions in the PFC.

Citing Articles

Neural deficits in a mouse model of PACS1 syndrome are corrected with PACS1- or HDAC6-targeting therapy.

Villar-Pazos S, Thomas L, Yang Y, Chen K, Lyles J, Deitch B Nat Commun. 2023; 14(1):6547.

PMID: 37848409 PMC: 10582149. DOI: 10.1038/s41467-023-42176-8.

The role of epigenetics in anxiety disorders.

Azargoonjahromi A Mol Biol Rep. 2023; 50(11):9625-9636.

PMID: 37804465 DOI: 10.1007/s11033-023-08787-6.

HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson's Disease Pathology in Mice.

Zhao J, He Y, Duan Y, Ma Y, Dong H, Zhang X Int J Mol Sci. 2023; 24(12).

PMID: 37373121 PMC: 10298689. DOI: 10.3390/ijms24129975.

Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors.

Hashimoto K, Ide S, Arata M, Nakata A, Ito A, Ito T ACS Med Chem Lett. 2022; 13(7):1077-1082.

PMID: 35859864 PMC: 9290043. DOI: 10.1021/acsmedchemlett.2c00081.

Epigenetic Approach to PTSD: In the Aspects of Rat Models.

Aykac A, Kalkan R Glob Med Genet. 2022; 9(1):7-13.

PMID: 35169777 PMC: 8837403. DOI: 10.1055/s-0041-1736633.

References

Bali P, Pranpat M, Bradner J, Balasis M, Fiskus W, Guo F . Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem. 2005; 280(29):26729-34. DOI: 10.1074/jbc.C500186200. View

Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V . (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev. 2006; 86(4):1151-78. DOI: 10.1152/physrev.00050.2005. View

Dompierre J, Godin J, Charrin B, Cordelieres F, King S, Humbert S . Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci. 2007; 27(13):3571-83. PMC: 6672116. DOI: 10.1523/JNEUROSCI.0037-07.2007. View

Rivieccio M, Brochier C, Willis D, Walker B, DAnnibale M, McLaughlin K . HDAC6 is a target for protection and regeneration following injury in the nervous system. Proc Natl Acad Sci U S A. 2009; 106(46):19599-604. PMC: 2780768. DOI: 10.1073/pnas.0907935106. View

Aoyagi S, Archer T . Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends Cell Biol. 2005; 15(11):565-7. DOI: 10.1016/j.tcb.2005.09.003. View

McEwen B . Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87(3):873-904. DOI: 10.1152/physrev.00041.2006. View

Liu W, Yuen E, Yan Z . The stress hormone corticosterone increases synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors via serum- and glucocorticoid-inducible kinase (SGK) regulation of the GDI-Rab4 complex. J Biol Chem. 2010; 285(9):6101-8. PMC: 2825404. DOI: 10.1074/jbc.M109.050229. View

Cadepond F, Jibard N, Hollenberg S, Giguere V, Evans R, Baulieu E . Heat shock protein 90 as a critical factor in maintaining glucocorticosteroid receptor in a nonfunctional state. J Biol Chem. 1991; 266(9):5834-41. View

Cerqueira J, Mailliet F, Almeida O, Jay T, Sousa N . The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci. 2007; 27(11):2781-7. PMC: 6672565. DOI: 10.1523/JNEUROSCI.4372-06.2007. View

10.

Joels M, Baram T . The neuro-symphony of stress. Nat Rev Neurosci. 2009; 10(6):459-66. PMC: 2844123. DOI: 10.1038/nrn2632. View

11.

Pratt W, Toft D . Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood). 2003; 228(2):111-33. DOI: 10.1177/153537020322800201. View

12.

Kovacs J, Murphy P, Gaillard S, Zhao X, Wu J, Nicchitta C . HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell. 2005; 18(5):601-7. DOI: 10.1016/j.molcel.2005.04.021. View

13.

Kazantsev A, Thompson L . Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov. 2008; 7(10):854-68. DOI: 10.1038/nrd2681. View

14.

Pandey U, Nie Z, Batlevi Y, McCray B, Ritson G, Nedelsky N . HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 2007; 447(7146):859-63. DOI: 10.1038/nature05853. View

15.

Chuang D, Leng Y, Marinova Z, Kim H, Chiu C . Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci. 2009; 32(11):591-601. PMC: 2771446. DOI: 10.1016/j.tins.2009.06.002. View

16.

Covington 3rd H, Maze I, LaPlant Q, Vialou V, Ohnishi Y, Berton O . Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009; 29(37):11451-60. PMC: 2775805. DOI: 10.1523/JNEUROSCI.1758-09.2009. View

17.

de Kloet E, Joels M, Holsboer F . Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005; 6(6):463-75. DOI: 10.1038/nrn1683. View

18.

Haggarty S, Koeller K, Wong J, Grozinger C, Schreiber S . Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A. 2003; 100(8):4389-94. PMC: 153564. DOI: 10.1073/pnas.0430973100. View

19.

Furumai R, Komatsu Y, Nishino N, Khochbin S, Yoshida M, Horinouchi S . Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc Natl Acad Sci U S A. 2001; 98(1):87-92. PMC: 14549. DOI: 10.1073/pnas.98.1.87. View

20.

Murphy P, Morishima Y, Kovacs J, Yao T, Pratt W . Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. J Biol Chem. 2005; 280(40):33792-9. DOI: 10.1074/jbc.M506997200. View