Evidence for Selective MicroRNAs and Their Effectors As Common Long-term Targets for the Actions of Mood Stabilizers

Overview

Journal Neuropsychopharmacology

Date 2008 Aug 16

PMID 18704095

Citations 152

Authors

Rulun Zhou

Peixiong Yuan

Yun Wang

Joshua G Hunsberger

Abdel Elkahloun

Yanling Wei

Patricia Damschroder-Williams

Jing Du

Guang Chen

Husseini K Manji

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) regulate messenger RNA (mRNA) translation in a sequence-specific manner and are emerging as critical regulators of central nervous system plasticity. We found hippocampal miRNA level changes following chronic treatment with mood stabilizers (lithium and valproate (VPA)). Several of these miRNAs were then confirmed by quantitative PCR: let-7b, let-7c, miR-128a, miR-24a, miR-30c, miR-34a, miR-221, and miR-144. The predicted effectors of these miRNAs are involved in neurite outgrowth, neurogenesis, and signaling of PTEN, ERK, and Wnt/beta-catenin pathways. Interestingly, several of these effector-coding genes are also genetic risk candidates for bipolar disorder. We provide evidence that treatment with mood stabilizers increases these potential susceptibility genes in vivo: dipeptidyl-peptidase 10, metabotropic glutamate receptor 7 (GRM7), and thyroid hormone receptor, beta. Treatment of primary cultures with lithium- or VPA-lowered levels of miR-34a and elevated levels of GRM7, a predicted effector of miR-34a. Conversely, miR-34a precursor treatment lowered GRM7 levels and treatment with a miR-34a inhibitor enhanced GRM7 levels. These data confirm that endogenous miR-34a regulates GRM7 levels and supports the notion that miR-34a contributes to the effects of lithium and VPA on GRM7. These findings are the first to demonstrate that miRNAs and their predicted effectors are targets for the action of psychotherapeutic drugs.

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References

Gould T, ODonnell K, Picchini A, Dow E, Chen G, Manji H . Generation and behavioral characterization of beta-catenin forebrain-specific conditional knock-out mice. Behav Brain Res. 2008; 189(1):117-25. PMC: 2676732. DOI: 10.1016/j.bbr.2007.12.028. View

Hobert O . Gene regulation by transcription factors and microRNAs. Science. 2008; 319(5871):1785-6. DOI: 10.1126/science.1151651. View

Yu I, Kim J, Lee S, Lee Y, Son H . Chronic lithium enhances hippocampal long-term potentiation, but not neurogenesis, in the aged rat dentate gyrus. Biochem Biophys Res Commun. 2003; 303(4):1193-8. DOI: 10.1016/s0006-291x(03)00494-7. View

Martin G, Schouest K, Kovvuru P, Spillane C . Prediction and validation of microRNA targets in animal genomes. J Biosci. 2007; 32(6):1049-52. DOI: 10.1007/s12038-007-0106-0. View

Manji H, Etcheberrigaray R, Chen G, Olds J . Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme. J Neurochem. 1993; 61(6):2303-10. DOI: 10.1111/j.1471-4159.1993.tb07474.x. View

Gould T, Einat H, ODonnell K, Picchini A, Schloesser R, Manji H . Beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors. Neuropsychopharmacology. 2007; 32(10):2173-83. DOI: 10.1038/sj.npp.1301338. View

Gould T, Manji H . The Wnt signaling pathway in bipolar disorder. Neuroscientist. 2002; 8(5):497-511. DOI: 10.1177/107385802237176. View

Laeng P, Pitts R, Lemire A, Drabik C, Weiner A, Tang H . The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. J Neurochem. 2004; 91(1):238-51. DOI: 10.1111/j.1471-4159.2004.02725.x. View

Gao F . Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 2007; 31(1):20-6. PMC: 3545480. DOI: 10.1016/j.tins.2007.10.004. View

10.

Chen G, Manji H, Hawver D, Wright C, Potter W . Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem. 1994; 63(6):2361-4. DOI: 10.1046/j.1471-4159.1994.63062361.x. View

11.

Belmaker R . Bipolar disorder. N Engl J Med. 2004; 351(5):476-86. DOI: 10.1056/NEJMra035354. View

12.

Kubota M, Kasahara T, Nakamura T, Ishiwata M, Miyauchi T, Kato T . Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial DNA defects. J Neurosci. 2006; 26(47):12314-24. PMC: 6675445. DOI: 10.1523/JNEUROSCI.3933-06.2006. View

13.

Hao Y, Creson T, Zhang L, Li P, Du F, Yuan P . Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. J Neurosci. 2004; 24(29):6590-9. PMC: 6729884. DOI: 10.1523/JNEUROSCI.5747-03.2004. View

14.

Gould T, QUIROZ J, Singh J, Zarate C, Manji H . Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers. Mol Psychiatry. 2004; 9(8):734-55. DOI: 10.1038/sj.mp.4001518. View

15.

Chen G, Zeng W, Yuan P, Huang L, Jiang Y, Zhao Z . The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem. 1999; 72(2):879-82. DOI: 10.1046/j.1471-4159.1999.720879.x. View

16.

Jacobsen J, Mork A . The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res. 2004; 1024(1-2):183-92. DOI: 10.1016/j.brainres.2004.07.065. View

17.

Hermeking H . p53 enters the microRNA world. Cancer Cell. 2007; 12(5):414-8. DOI: 10.1016/j.ccr.2007.10.028. View

18.

Shaltiel G, Maeng S, Malkesman O, Pearson B, Schloesser R, Tragon T . Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania. Mol Psychiatry. 2008; 13(9):858-72. PMC: 2804880. DOI: 10.1038/mp.2008.20. View

19.

Einat H, Yuan P, Gould T, Li J, Du J, Zhang L . The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci. 2003; 23(19):7311-6. PMC: 6740453. View

20.

Frey B, Andreazza A, Cereser K, Martins M, Valvassori S, Reus G . Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania. Life Sci. 2006; 79(3):281-6. DOI: 10.1016/j.lfs.2006.01.002. View