Thinking small: Towards microRNA-based therapeutics for anxiety disorders

Expert Opinion on Investigational Drugs

Volumn 24, Issue 4, 2015, Pages 529-542

  Scott, Karen A ^a,b   Hoban, Alan E ^a,b   Clarke, Gerard ^a,b   Moloney, Gerard M ^a,b   Dinan, Timothy G ^a,b   Cryan, John F ^a,b  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Anxiety disorders; Clinical trials; Drugs; MicroRNA; Preclinical models

Indexed keywords

MICRORNA; ANXIOLYTIC AGENT;

ALZHEIMER DISEASE; ANXIETY; ANXIETY DISORDER; BIPOLAR DISORDER; CANCER RESEARCH; CELL POPULATION; CLINICAL STUDY; DEGENERATIVE DISEASE; DEPRESSION; DOWN REGULATION; ENVIRONMENTAL ENRICHMENT; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE EXPRESSION; GENETICS; HIGH RISK BEHAVIOR; HUMAN; MAJOR DEPRESSION; MENTAL DISEASE; MOOD DISORDER; MORTALITY; POSTTRAUMATIC STRESS DISORDER; REVIEW; SCHIZOAFFECTIVE PSYCHOSIS; SIDE EFFECT; TRAUMATIC BRAIN INJURY; UPREGULATION; ANIMAL; ANXIETY DISORDERS; BLOOD BRAIN BARRIER; COST OF ILLNESS; METABOLISM; MOLECULARLY TARGETED THERAPY; QUALITY OF LIFE;

ANIMALS; ANTI-ANXIETY AGENTS; ANXIETY DISORDERS; BLOOD-BRAIN BARRIER; COST OF ILLNESS; HUMANS; MICRORNAS; MOLECULAR TARGETED THERAPY; QUALITY OF LIFE;

EID: 84924726671     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2014.997873     Document Type: Review

References (113)

1. Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc 2009;18(1):23-33
2. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6):593-602
3. Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nat Reviews Drug Discov 2013;12(9):667-87
4. American Psychiatric Association, American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders: DSM-5. 5th edition. American Psychiatric Association; Washington, DC: 2013
5. Cryan JF, Sweeney FF. The age of anxiety: role of animal models of anxiolytic action in drug discovery. Br J Pharmacol 2011;164(4):1129-61
6. Kessler RC, McLaughlin KA, Green JG, et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry 2010;197(5):378-85
7. Le-Niculescu H, Balaraman Y, Patel SD, et al. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms. Transl Psychiatry 2011;1:e9
8. Hoge CW, Castro CA, Messer SC, et al. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med 2004;351(1):13-22
9. Yehuda R, Vermetten E, McFarlane AC, et al. PTSD in the military: special considerations for understanding prevalence, pathophysiology and treatment following deployment. Eur J Psychotraumatol 2014;5
10. Domschke K, Dannlowski U. Imaging genetics of anxiety disorders. Neuroimage 2010;53(3):822-31
11. Norrholm SD, Ressler KJ. Genetics of anxiety and trauma-related disorders. Neuroscience 2009;164(1):272-87
12. Erhardt A, Spoormaker VI. Translational approaches to anxiety: focus on genetics, fear extinction and brain imaging. Curr Psychiatry Rep 2013;15(12):417
13. Ono S, Domschke K, Deckert J. Genomic structural variation in affective, anxiety, and stress-related disorders. J Neural Transm 2014. [Epub ahead of print]
14. Combs H, Markman J. Anxiety disorders in primary care. Med Clin North Am 2014;98(5):1007-23
15. Bukalo O, Pinard CR, Holmes A. Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders. Br J Pharmacol 2014;171(20):4690-718
16. Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry 2010;71(7):839-54
17. Mohler H. The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology 2012;62(1):42-53
18. Sinclair LI, Nutt DJ. Anxiolytics. Handb Clin Neurol 2012;106:669-79
19. Stewart AM, Kalueff AV. Anxiolytic drug discovery: what are the novel approaches and how can we improve them? Expert Opin Drug Discov 2014;9(1):15-26
20. O'Connor RM, Finger BC, Flor PJ, et al. Metabotropic glutamate receptor 7: at the interface of cognition and emotion. Eur J Pharmacol 2010;639(1-3):123-31
21. McGrath LM, Weill S, Robinson EB, et al. Bringing a developmental perspective to anxiety genetics. Dev Psychopathol 2012;24(4):1179-93
22. Donner NC, Montoya CD, Lukkes JL, et al. Chronic non-invasive corticosterone administration abolishes the diurnal pattern of tph2 expression. Psychoneuroendocrinology 2012;37(5):645-61
23. Tardito D, Mallei A, Popoli M. Lost in translation. New unexplored avenues for neuropsychopharmacology: epigenetics and microRNAs. Expert Opin Investig Drugs 2013;22(2):217-33
24. Narayan P, Dragunow M. Pharmacology of epigenetics in brain disorders. Br J Pharmacol 2010;159(2):285-303
25. Klengel T, Mehta D, Anacker C, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 2013;16(1):33-41
26. Binder EB. The role of FKBP5, a cochaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 2009;34(Suppl 1)):S186-95
27. Almeida MI, Reis RM, Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res 2011;717(1-2):1-8
28. Kong YW, Ferland-McCollough D, Jackson TJ, et al. microRNAs in cancer management. Lancet Oncol 2012;13(6):e249-58
29. Nana-Sinkam SP, Croce CM. Clinical applications for microRNAs in cancer. Clin Pharmacol Ther 2013;93(1):98-104
30. O'Connor RM, Dinan TG, Cryan JF. Little things on which happiness depends: microRNAs as novel therapeutic targets for the treatment of anxiety and depression. Mol Psychiatry 2012;17(4):359-76
31. O'Connor RM, Grenham S, Dinan TG, et al. microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus. Int J Neuropsychopharmacol 2013;16(8):1885-92
32. Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA 2012;3(3):311-30
33. Ceman S, Saugstad J. MicroRNAs: metacontrollers of gene expression in synaptic activity emerge as genetic and diagnostic markers of human disease. Pharmacol Ther 2011;130(1):26-37
34. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136(2):215-33
35. Lee D, Shin C. MicroRNA-target interactions: new insights from genomewide approaches. Ann N Y Acad Sci 2012;1271:118-28
36. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004;5(7):522-31
37. Miller BH, Wahlestedt C. MicroRNA dysregulation in psychiatric disease. Brain Res 2010;1338:89-99
38. Broderick JA, Zamore PD. MicroRNA therapeutics. Gene Ther 2011;18(12):1104-10
39. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005;433(7027):769-73
40. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet 2012;13(5):358-69
41. Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol 2011;80(2):193-208
42. McEwen BS, Getz L. Lifetime experiences, the brain and personalized medicine: an integrative perspective. Metabolism 2013;62(Suppl 1):S20-6
43. Chan AW, Kocerha J. The Path to microRNA therapeutics in psychiatric and neurodegenerative disorders. Front Genet 2012;3:82
44. Wu Y, Crawford M, Mao Y, et al. Therapeutic delivery of microRNA-29b by cationic lipoplexes for lung cancer. Mol Ther Nucleic Acids 2013;2:e84
45. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013;12(11):847-65
46. Hu J, Xu Y, Hao J, et al. MiR-122 in hepatic function and liver diseases. Protein Cell 2012;3(5):364-71
47. van der Ree MH, van der Meer AJ, de Bruijne J, et al. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Res 2014;111:53-9
48. Rogaev EI. Small RNAs in human brain development and disorders. Biochemistry (Mosc) 2005;70(12):1404-7
49. Sonntag KC, Wahlestedt C. RNA mechanisms in CNS systems and disorders. Brain Res 2010;1338:1-2
50. Bocchio-Chiavetto L, Maffioletti E, Bettinsoli P, et al. Blood microRNA changes in depressed patients during antidepressant treatment. Eur Neuropsychopharmacol 2013;23(7):602-11
51. Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. The WHO World Mental Health (WMH) Surveys. Psychiatrie 2009;6(1):5-9
52. Kolshus E, Dalton VS, Ryan KM, et al. When less is more-microRNAs and psychiatric disorders. Acta Psychiatr Scand 2014;129(4):241-56
53. Ojo JO, Greenberg MB, Leary P, et al. Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury. Front Behav Neurosci 2014;8:213
54. Honda M, Kuwano Y, Katsuura-Kamano S, et al. Chronic academic stress increases a group of microRNAs in peripheral blood. PLoS One 2013;8(10):e75960
55. Katsuura S, Kuwano Y, Yamagishi N, et al. MicroRNAs miR-144/144 and miR-16 in peripheral blood are potential biomarkers for naturalistic stress in healthy Japanese medical students. Neurosci Lett 2012;516(1):79-84
56. Muinos-Gimeno M, Espinosa-Parrilla Y, Guidi M, et al. Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways. Biol Psychiatry 2011;69(6):526-33
57. Jin XF, Wu N, Wang L, et al. Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases. Cell Mol Neurobiol 2013;33(5):601-13
58. Liang H, Gong F, Zhang S, et al. The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids. Wiley Interdiscip Rev RNA 2014;5(2):285-300
59. Liu R, Zhang C, Hu Z, et al. A fivemicroRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 2011;47(5):784-91
60. Patel RS, Jakymiw A, Yao B, et al. High resolution of microRNA signatures in human whole saliva. Arch Oral Biol 2011;56(12):1506-13
61. Chen X, Liang H, Zhang J, et al. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol 2012;22(3):125-32
62. Etheridge A, Lee I, Hood L, et al. Extracellular microRNA: a new source of biomarkers. Mutat Res 2011;717(1-2):85-90
63. Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. Proteomics 2008;8(19):4083-99
64. Pritchard CC, Kroh E, Wood B, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila) 2012;5(3):492-7
65. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable bloodbased markers for cancer detection. Proc Natl Acad Sci USA 2008;105(30):10513-18
66. Meza-Sosa KF, Valle-Garcia D, Pedraza-Alva G, et al. Role of microRNAs in central nervous system development and pathology. J Neurosci Res 2012;90(1):1-12
67. Rao P, Benito E, Fischer A. MicroRNAs as biomarkers for CNS disease. Front Mol Neurosci 2013;6:39
68. Haghikia A, Haghikia A, Hellwig K, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a casecontrol study. Neurology 2012;79(22):2166-70
69. Kiko T, Nakagawa K, Tsuduki T, et al. MicroRNAs in plasma and cerebrospinal fluid as potential markers for Alzheimer's disease. J Alzheimers Dis 2014;39(2):253-9
70. Liu CG, Song J, Zhang YQ, et al. MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease. Mol Med Rep 2014;10(5):2395-400
71. Sorensen SS, Nygaard AB, Nielsen MY, et al. miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. Transl Stroke Res 2014;5(6):711-18
72. Hirschfeld RM. The comorbidity of major depression and anxiety disorders: recognition and management in primary care. Prim Care Companion J Clin Psychiatry 2001;3(6):244-54
73. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6):617-27
74. Issler O, Haramati S, Paul ED, et al. MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron 2014;83(2):344-60
75. Lopez JP, Lim R, Cruceanu C, et al. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat Med 2014;20(7):764-8
76. Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat Neurosci 2010;13(10):1161-9
77. Blanchard RJ, McKittrick CR, Blanchard DC. Animal models of social stress: effects on behavior and brain neurochemical systems. Physiol Behav 2001;73(3):261-71
78. Neumann ID, Wegener G, Homberg JR, et al. Animal models of depression and anxiety: what do they tell us about human condition? Prog Neuropsychopharmacol Biol Psychiatry 2011;35(6):1357-75
79. Cryan JF, Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 2005;4(9):775-90
80. Schmidt U, Herrmann L, Hagl K, et al. Therapeutic action of fluoxetine is associated with a reduction in prefrontal cortical miR-1971 expression levels in a mouse model of posttraumatic stress disorder. Front Psychiatry 2013;4:66
81. Durairaj RV, Koilmani ER. Environmental enrichment modulates glucocorticoid receptor expression and reduces anxiety in Indian field male mouse Mus booduga through upregulation of microRNA-124a. Gen Comp Endocrinol 2014;199:26-32
82. Mannironi C, Camon J, De Vito F, et al. Acute stress alters amygdala microRNA miR-135a and miR-124 expression: inferences for corticosteroid dependent stress response. PLoS One 2013;8(9):e73385
83. Meerson A, Cacheaux L, Goosens KA, et al. Changes in brain MicroRNAs contribute to cholinergic stress reactions. J Mol Neurosci 2010;40(1-2):47-55
84. Griggs EM, Young EJ, Rumbaugh G, et al. MicroRNA-182 regulates amygdala-dependent memory formation. J Neurosci 2013;33(4):1734-40
85. Lin Q, Wei W, Coelho CM, et al. The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Nat Neurosci 2011;14(9):1115-17
86. Ragu Varman D, Marimuthu G, Rajan KE. Environmental enrichment upregulates micro-RNA-183 and alters acetylcholinesterase splice variants to reduce anxiety-like behavior in the little Indian field mouse (Mus booduga). J Neurosci Res 2013;91(3):426-35
87. Shaltiel G, Hanan M, Wolf Y, et al. Hippocampal microRNA-132 mediates stress-inducible cognitive deficits through its acetylcholinesterase target. Brain Struct Funct 2013;218(1):59-72
88. Zhou R, Yuan P, Wang Y, et al. Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology 2009;34(6):1395-405
89. Zovoilis A, Agbemenyah HY, Agis-Balboa RC, et al. MicroRNA-34c is a novel target to treat dementias. EMBO J 2011;30(20):4299-308
90. Dias BG, Goodman JV, Ahluwalia R, et al. Amygdala-dependent fear memory consolidation via miR-34a and notch signaling. Neuron 2014;83(4):906-18 . An elegant study implicating amygdalar miR-34c levels in development of anxiety.
91. Savignac HM, Finger BC, Pizzo RC, et al. Increased sensitivity to the effects of chronic social defeat stress in an innately anxious mouse strain. Neuroscience 2011;192:524-36
92. Slattery DA, Uschold N, Magoni M, et al. Behavioural consequences of two chronic psychosocial stress paradigms: anxiety without depression. Psychoneuroendocrinology 2012;37(5):702-14
93. Hartmann J, Wagner KV, Liebl C, et al. The involvement of FK506-binding protein 51 (FKBP5) in the behavioral and neuroendocrine effects of chronic social defeat stress. Neuropharmacology 2012;62(1):332-9
94. Vialou V, Maze I, Renthal W, et al. Serum response factor promotes resilience to chronic social stress through the induction of DeltaFosB. J Neurosci 2010;30(43):14585-92
95. Haramati S, Navon I, Issler O, et al. MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. J Neurosci 2011;31(40):14191-203
96. Parsons MJ, Grimm C, Paya-Cano JL, et al. Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains. BMC Genomics 2012;13:476
97. Parsons MJ, Grimm CH, Paya-Cano JL, et al. Using hippocampal microRNA expression differences between mouse inbred strains to characterise miRNA function. Mamm Genome 2008;19(7-8):552-60
98. Uchida S, Hara K, Kobayashi A, et al. Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents. J Neurosci 2010;30(45):15007-18
99. Hamilton DE, Cooke CL, Carter BS, et al. Basal microRNA expression patterns in reward circuitry of selectively bred high-responder and low-responder rats vary by brain region and genotype. Physiol Genomics 2014;46(8):290-301
100. Rinaldi A, Vincenti S, De Vito F, et al. Stress induces region specific alterations in microRNAs expression in mice. Behav Brain Res 2010;208(1):265-9
101. Mehta N, Cheng HY. Micro-managing the circadian clock: the role of microRNAs in biological timekeeping. J Mol Biol 2013;425(19):3609-24
102. Mestdagh P, Hartmann N, Baeriswyl L, et al. Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nat Methods 2014;11(8):809-15
103. Balakathiresan NS, Chandran R, Bhomia M, et al. Serum and amygdala microRNA signatures of posttraumatic stress: fear correlation and biomarker potential. J Psychiatr Res 2014;57:65-73
104. Jiang X, Du L, Wang L, et al. Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer. Int J Cancer 2015;136(4):854-62
105. Yang C, Wang C, Chen X, et al. Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int J Cancer 2013;132(1):116-27
106. Zhang Y, Wang Z, Gemeinhart RA. Progress in microRNA delivery. J Control Release 2013;172(3):962-74
107. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011;12(12):861-74
108. Lu Y, Xiao J, Lin H, et al. A single antimicroRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference. Nucleic Acids Res 2009;37(3):e24
109. Elmen J, Lindow M, Schutz S, et al. LNA-mediated microRNA silencing in non-human primates. Nature 2008;452(7189):896-9
110. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013;368(18):1685-94
111. Yang B, Li S, Wang H, et al. Global CNS transduction of adult mice by intravenously delivered rAAVrh.8 and rAAVrh.10 and nonhuman primates by rAAVrh.10. Mol Ther 2014;22(7):1299-309
112. Iida A, Takino N, Miyauchi H, et al. Systemic delivery of tyrosine-mutant AAV vectors results in robust transduction of neurons in adult mice. Biomed Res Int 2013;2013:974819
113. Smalheiser NR, Lugli G, Rizavi HS, et al. MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness. Int Journal of Neuropsychopharmacology 2011;14(10):1315-25