Epigenetic Treatments for Cognitive Impairments

Overview

Journal Neuropsychopharmacology

Date 2011 May 20

PMID 21593731

Citations 36

Authors

Jeremy J Day

J David Sweatt

Affiliations

Soon will be listed here.

Abstract

Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In this review, we will examine how epigenetic mechanisms contribute to cognition, consider how changes in these mechanisms may lead to cognitive impairments in a range of disorders and discuss the potential utility of therapeutic treatments that target epigenetic machinery. Finally, we will comment on a number of caveats associated with interpreting epigenetic changes and using epigenetic treatments, and suggest future directions for research in this area that will expand our understanding of the epigenetic changes underlying cognitive disorders.

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References

Provost P . MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases. Brain Res. 2010; 1338:58-66. PMC: 2896967. DOI: 10.1016/j.brainres.2010.03.069. View

Penner M, Roth T, Barnes C, Sweatt J . An epigenetic hypothesis of aging-related cognitive dysfunction. Front Aging Neurosci. 2010; 2:9. PMC: 2874394. DOI: 10.3389/fnagi.2010.00009. View

Santini E, Alcacer C, Cacciatore S, Heiman M, Herve D, Greengard P . L-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. J Neurochem. 2009; 108(3):621-33. DOI: 10.1111/j.1471-4159.2008.05831.x. View

Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L . Recovery of learning and memory is associated with chromatin remodelling. Nature. 2007; 447(7141):178-82. DOI: 10.1038/nature05772. View

Adachi M, Autry A, Covington 3rd H, Monteggia L . MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. J Neurosci. 2009; 29(13):4218-27. PMC: 3005250. DOI: 10.1523/JNEUROSCI.4225-08.2009. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Gregg C, Zhang J, Butler J, Haig D, Dulac C . Sex-specific parent-of-origin allelic expression in the mouse brain. Science. 2010; 329(5992):682-5. PMC: 2997643. DOI: 10.1126/science.1190831. View

Shahbazian M, Young J, Spencer C, Antalffy B, Noebels J, Armstrong D . Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron. 2002; 35(2):243-54. DOI: 10.1016/s0896-6273(02)00768-7. View

Merienne K, Pannetier S, Harel-Bellan A, Sassone-Corsi P . Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities. Mol Cell Biol. 2001; 21(20):7089-96. PMC: 99884. DOI: 10.1128/MCB.21.20.7089-7096.2001. View

10.

Fontan-Lozano A, Suarez-Pereira I, Horrillo A, Del-Pozo-Martin Y, Hmadcha A, Carrion A . Histone H1 poly[ADP]-ribosylation regulates the chromatin alterations required for learning consolidation. J Neurosci. 2010; 30(40):13305-13. PMC: 6634736. DOI: 10.1523/JNEUROSCI.3010-10.2010. View

11.

Akbarian S, Huang H . Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry. 2008; 65(3):198-203. PMC: 2637452. DOI: 10.1016/j.biopsych.2008.08.015. View

12.

Hernandez A, Wolk J, Hu J, Liu J, Kurosu T, Schwartz J . Poly-(ADP-ribose) polymerase-1 is necessary for long-term facilitation in Aplysia. J Neurosci. 2009; 29(30):9553-62. PMC: 6666525. DOI: 10.1523/JNEUROSCI.1512-09.2009. View

13.

Koshibu K, Graff J, Beullens M, Heitz F, Berchtold D, Russig H . Protein phosphatase 1 regulates the histone code for long-term memory. J Neurosci. 2009; 29(41):13079-89. PMC: 6665317. DOI: 10.1523/JNEUROSCI.3610-09.2009. View

14.

Tsukada Y, Fang J, Erdjument-Bromage H, Warren M, Borchers C, Tempst P . Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2005; 439(7078):811-6. DOI: 10.1038/nature04433. View

15.

Messner S, Altmeyer M, Zhao H, Pozivil A, Roschitzki B, Gehrig P . PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res. 2010; 38(19):6350-62. PMC: 2965223. DOI: 10.1093/nar/gkq463. View

16.

Chahrour M, Jung S, Shaw C, Zhou X, Wong S, Qin J . MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008; 320(5880):1224-9. PMC: 2443785. DOI: 10.1126/science.1153252. View

17.

Renthal W, Nestler E . Epigenetic mechanisms in drug addiction. Trends Mol Med. 2008; 14(8):341-50. PMC: 2753378. DOI: 10.1016/j.molmed.2008.06.004. View

18.

Moretti P, Bouwknecht J, Teague R, Paylor R, Zoghbi H . Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum Mol Genet. 2004; 14(2):205-20. DOI: 10.1093/hmg/ddi016. View

19.

Roth T, Lubin F, Funk A, Sweatt J . Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009; 65(9):760-9. PMC: 3056389. DOI: 10.1016/j.biopsych.2008.11.028. View

20.

Chwang W, Arthur J, Schumacher A, Sweatt J . The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation. J Neurosci. 2007; 27(46):12732-42. PMC: 5724774. DOI: 10.1523/JNEUROSCI.2522-07.2007. View