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miRNA regulation of social and anxiety-related behaviour

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Abstract

Neuropsychiatric disorders, including autism spectrum disorders (ASD) and anxiety disorders are characterized by a complex range of symptoms, including social behaviour and cognitive deficits, depression and repetitive behaviours. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their aetiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as a new gene regulatory layer in the pathophysiology of mental illness. These small RNAs can bind to the 3′-UTR of mRNA thereby negatively regulating gene expression at the post-transcriptional level. Their ability to regulate hundreds of target mRNAs simultaneously predestines them to control the activity of entire cellular pathways, with obvious implications for the regulation of complex processes such as animal behaviour. There is growing evidence to suggest that numerous miRNAs are dysregulated in pathophysiology of neuropsychiatric disorders, and there is strong genetic support for the association of miRNA genes and their targets with several of these conditions. This review attempts to cover the most relevant microRNAs for which an important contribution to the control of social and anxiety-related behaviour has been demonstrated by functional studies in animal models. In addition, it provides an overview of recent expression profiling and genetic association studies in human patient-derived samples in an attempt to highlight the most promising candidates for biomarker discovery and therapeutic intervention.

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Abbreviations

AAV:

Adeno associated virus

AChE:

Acetyl cholinesterase

AGO:

Argonaute

AMPAR:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

AS:

Acute stress

ASD:

Autism spectrum disorder

BChE:

Butyrylcholinesterase

BD:

Bipolar disorder

BDNF:

Brain-derived neurotrophic factor

BLA:

Basolateral amygdala

CA1:

Cornu Ammonis area 1

Cas9:

CRISPR associated protein 9

cAMP:

Cyclic adenosine triphosphate

CCKBR:

Cholecystokinin B receptor

CeA:

Central amygdala

cGMP:

Cyclic guanine triphosphate

CHMP2B:

Charged multivesicular body protein 2b

circRNA:

Circular RNA

CNR1:

Cannabinoid receptor type 1

CNV:

Copy number variation

CRF:

Corticotrophin releasing factor

CRFR1:

Corticotrophin releasing factor receptor 1

CRHR1:

Corticotrophin releasing hormone receptor 1

CRISPR:

Clustered regularly interspaced short palindromic repeats

CRS:

Chronic restraint stress

DG:

Dentate gyrus

DGCR8:

DiGeorge syndrome chromosomal region 8

DRD2:

Dopamine receptor D 2

DSM-V:

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

Egr-1:

Early growth response protein 1

EPAC:

Exchange factor directly activated by cAMP

EPM:

Elevated plus maze

Ezh2:

Enhancer of zeste homolog 2

F1:

Filial 1

Foxp2:

Forkhead box protein P2

FTD:

Frontotemporal dementia

GABA:

γ-Aminobutyric acid

GABRA6:

Gamma-aminobutyric acid receptor subunit alpha-6

GluA:

Glutamate receptor, AMPA type

GluN2A:

Glutamate receptor NMDA type 2A

GluR:

Glutamate receptor

GR:

Glucocorticoid receptor

GRIA:

Glutamate receptor

GRM7:

Metabotropic glutamate receptor 7

GWAS:

Genome-wide association study

Hc:

Hippocampus

hNSC:

Human neural stem cell

HPA:

Hypothalamus–pituitary–adrenal axis

5-HT2C:

5-Hydroxytryptamine 2C

HTR2C:

5-Hydroxytryptamine receptor 2C

ID:

Intellectual disability

IKBKE:

Inhibitor of nuclear factor kappa-B kinase subunit epsilon

IL-6:

Interleukin-6

iPSC:

Induced pluripotent stem cell

JAK:

Janus kinase

KO:

Knockout

lncRNA:

Long non-coding RNA

LTD:

Long term depression

LTP:

Long term potentiation

MAOA:

Monoamine oxidase A

MAP1B:

Microtubule-associated protein 1B

MeCP2:

Methyl CpG binding protein 2

mGluR:

Metabotropic glutamate receptor

miRNA:

Micro RNA

mPFC:

Medial prefrontal cortex

mRNA:

Messenger RNA

MSUS:

Maternal separation, unexpected stress

ncRNA:

Non-coding RNA

NMDA:

N-Methyl-d-aspartate

OCD:

Obsessive–compulsive disorder

PCR:

Polymerase chain reaction

PD:

Panic disorder

Pde10a:

Phosphodiesterase 10A

PI3K:

Phosphoinositide 3-kinase

piRNA:

Piwi-interacting RNA

POMC:

Pro-opiomelanocortin

Pre-miRNA:

Precursor micro RNA

Pri-miRNA:

Primary micro RNA

PSD95:

Post-synaptic density 95

PTEN:

Phosphatase and tensin homolog

PTSD:

Post-traumatic stress disorder

PVN:

Paraventricular nucleus

Rap1:

Ras-related protein 1

RapGEFs:

Rap guanine nucleotide exchange factor

RGS2:

Regulator of G-protein signaling 2

RISC:

RNA induced silencing complex

RNA:

Ribonucleic acid

RNase:

Ribonuclease

Sgk1:

Serum and glucocorticoid-regulated kinase 1

Sirt1:

Sirtuin 1

smFISH:

Single-molecule fluorescent in situ hybridization

SNP:

Single nucleotide polymorphism

STAT:

Signal transducer and activator of transcription

TNF-a:

Tumor necrosis factor alpha

TRBP:

TAR RNA binding protein

USV:

Ultrasonic vocalization

UTR:

Untranslated region

References

  1. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854. https://doi.org/10.1016/0092-8674(93)90529-y

    Article  CAS  Google Scholar 

  2. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862. https://doi.org/10.1016/0092-8674(93),90530-4

    Article  CAS  Google Scholar 

  3. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906. https://doi.org/10.1038/35002607

    Article  CAS  Google Scholar 

  4. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15(8):509–524. https://doi.org/10.1038/nrm3838

    Article  CAS  Google Scholar 

  5. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610. https://doi.org/10.1038/nrg2843

    Article  CAS  Google Scholar 

  6. Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11(3):228–234. https://doi.org/10.1038/ncb0309-228

    Article  CAS  Google Scholar 

  7. Meister G (2013) Argonaute proteins: functional insights and emerging roles. Nat Rev Genet 14(7):447–459. https://doi.org/10.1038/nrg3462

    Article  CAS  Google Scholar 

  8. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9(2):102–114. https://doi.org/10.1038/nrg2290

    Article  CAS  Google Scholar 

  9. Hammond SM (2015) An overview of microRNAs. Adv Drug Deliv Rev 87:3–14. https://doi.org/10.1016/j.addr.2015.05.001

    Article  CAS  Google Scholar 

  10. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139. https://doi.org/10.1038/nrm2632

    Article  CAS  Google Scholar 

  11. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ (2010) A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465(7298):584–589. https://doi.org/10.1038/nature09092

    Article  CAS  Google Scholar 

  12. Abdelfattah AM, Park C, Choi MY (2014) Update on non-canonical microRNAs. Biomol Concepts 5(4):275–287. https://doi.org/10.1515/bmc-2014-0012

    Article  CAS  Google Scholar 

  13. Baskerville S, Bartel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11(3):241–247. https://doi.org/10.1261/rna.7240905

    Article  CAS  Google Scholar 

  14. Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294(5543):858–862. https://doi.org/10.1126/science.1065062

    Article  CAS  Google Scholar 

  15. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294(5543):853–858. https://doi.org/10.1126/science.1064921

    Article  CAS  Google Scholar 

  16. Lee RC, Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294(5543):862–864. https://doi.org/10.1126/science.1065329

    Article  CAS  Google Scholar 

  17. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002

    Article  CAS  Google Scholar 

  18. Huntzinger E, Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 12(2):99–110. https://doi.org/10.1038/nrg2936

    Article  CAS  Google Scholar 

  19. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289. https://doi.org/10.1038/nature04367

    Article  CAS  Google Scholar 

  20. Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJ, Kane C, Hubel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 11(6):705–716. https://doi.org/10.1038/ncb1876

    Article  CAS  Google Scholar 

  21. Buiting K, Williams C, Horsthemke B (2016) Angelman syndrome—insights into a rare neurogenetic disorder. Nat Rev Neurol 12(10):584–593. https://doi.org/10.1038/nrneurol.2016.133

    Article  CAS  Google Scholar 

  22. Lackinger M, Sungur AO, Daswani R, Soutschek M, Bicker S, Stemmler L, Wust T, Fiore R, Dieterich C, Schwarting RK, Wohr M, Schratt G (2019) A placental mammal-specific microRNA cluster acts as a natural brake for sociability in mice. EMBO Rep. https://doi.org/10.15252/embr.201846429

    Article  Google Scholar 

  23. Yin CL, Chen HI, Li LH, Chien YL, Liao HM, Chou MC, Chou WJ, Tsai WC, Chiu YN, Wu YY, Lo CZ, Wu JY, Chen YT, Gau SS (2016) Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder. Mol Autism 7:23. https://doi.org/10.1186/s13229-016-0087-7

    Article  CAS  Google Scholar 

  24. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EGP, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477. https://doi.org/10.1093/brain/awr179

    Article  Google Scholar 

  25. Gao FB (2010) Context-dependent functions of specific microRNAs in neuronal development. Neural Dev. https://doi.org/10.1186/1749-8104-5-25

    Article  Google Scholar 

  26. Gascon E, Lynch K, Ruan HY, Almeida S, Verheyden JM, Seeley WW, Dickson DW, Petrucelli L, Sun DQ, Jiao J, Zhou HR, Jakovcevski M, Akbarian S, Yao WD, Gao FB (2014) Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemp oral dementia. Nat Med 20(12):1444–1451. https://doi.org/10.1038/nm.3717

    Article  CAS  Google Scholar 

  27. Yang Y, Shu X, Liu D, Shang Y, Wu Y, Pei L, Xu X, Tian Q, Zhang J, Qian K, Wang YX, Petralia RS, Tu W, Zhu LQ, Wang JZ, Lu Y (2012) EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation. Neuron 73(4):774–788. https://doi.org/10.1016/j.neuron.2012.02.003

    Article  CAS  Google Scholar 

  28. Bahi A (2017) Hippocampal BDNF overexpression or microR124a silencing reduces anxiety- and autism-like behaviors in rats. Behav Brain Res 326:281–290. https://doi.org/10.1016/j.bbr.2017.03.010

    Article  CAS  Google Scholar 

  29. Cheng Y, Wang ZM, Tan WQ, Wang XN, Li YJ, Bai B, Li YX, Zhang SF, Yan HL, Chen ZL, Liu CM, Mi TW, Xia ST, Zhou ZK, Liu A, Tang GB, Liu C, Dai ZJ, Wang YY, Wang H, Wang XS, Kang YH, Lin L, Chen ZP, Xie NN, Sun QM, Xie W, Peng JM, Chen DH, Teng ZQ, Jin P (2018) Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a. Nat Neurosci 21(12):1689. https://doi.org/10.1038/s41593-018-0261-7

    Article  CAS  Google Scholar 

  30. Olde Loohuis NF, Ba W, Stoerchel PH, Kos A, Jager A, Schratt G, Martens GJ, van Bokhoven H, Nadif Kasri N, Aschrafi A (2015) MicroRNA-137 controls AMPA-receptor-mediated transmission and mGluR-dependent LTD. Cell Rep 11(12):1876–1884. https://doi.org/10.1016/j.celrep.2015.05.040

    Article  CAS  Google Scholar 

  31. Carter MT, Nikkel SM, Fernandez BA, Marshall CR, Noor A, Lionel AC, Prasad A, Pinto D, Joseph-George AM, Noakes C, Fairbrother-Davies C, Roberts W, Vincent J, Weksberg R, Scherer SW (2011) Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder. Clin Genet 80(5):435–443. https://doi.org/10.1111/j.1399-0004.2010.01578.x

    Article  CAS  Google Scholar 

  32. Willemsen MH, Valles A, Kirkels LA, Mastebroek M, Olde Loohuis N, Kos A, Wissink-Lindhout WM, de Brouwer AP, Nillesen WM, Pfundt R, Holder-Espinasse M, Vallee L, Andrieux J, Coppens-Hofman MC, Rensen H, Hamel BC, van Bokhoven H, Aschrafi A, Kleefstra T (2011) Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability. J Med Genet 48(12):810–818. https://doi.org/10.1136/jmedgenet-2011-100294

    Article  CAS  Google Scholar 

  33. Ripke S, O'Dushlaine C, Chambert K, Moran JL, Kahler AK, Akterin S, Bergen SE, Collins AL, Crowley JJ, Fromer M, Kim Y, Lee SH, Magnusson PK, Sanchez N, Stahl EA, Williams S, Wray NR, Xia K, Bettella F, Borglum AD, Bulik-Sullivan BK, Cormican P, Craddock N, de Leeuw C, Durmishi N, Gill M, Golimbet V, Hamshere ML, Holmans P, Hougaard DM, Kendler KS, Lin K, Morris DW, Mors O, Mortensen PB, Neale BM, O'Neill FA, Owen MJ, Milovancevic MP, Posthuma D, Powell J, Richards AL, Riley BP, Ruderfer D, Rujescu D, Sigurdsson E, Silagadze T, Smit AB, Stefansson H, Steinberg S, Suvisaari J, Tosato S, Verhage M, Walters JT, Multicenter Genetic Studies of Schizophrenia C, Levinson DF, Gejman PV, Kendler KS, Laurent C, Mowry BJ, O'Donovan MC, Owen MJ, Pulver AE, Riley BP, Schwab SG, Wildenauer DB, Dudbridge F, Holmans P, Shi J, Albus M, Alexander M, Campion D, Cohen D, Dikeos D, Duan J, Eichhammer P, Godard S, Hansen M, Lerer FB, Liang KY, Maier W, Mallet J, Nertney DA, Nestadt G, Norton N, O'Neill FA, Papadimitriou GN, Ribble R, Sanders AR, Silverman JM, Walsh D, Williams NM, Wormley B, Psychosis Endophenotypes International C, Arranz MJ, Bakker S, Bender S, Bramon E, Collier D, Crespo-Facorro B, Hall J, Iyegbe C, Jablensky A, Kahn RS, Kalaydjieva L, Lawrie S, Lewis CM, Lin K, Linszen DH, Mata I, McIntosh A, Murray RM, Ophoff RA, Powell J, Rujescu D, Van Os J, Walshe M, Weisbrod M, Wiersma D, Wellcome Trust Case Control C, Donnelly P, Barroso I, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin AP, Deloukas P, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Spencer CC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson RD, Strange A, Su Z, Vukcevic D, Donnelly P, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Tashakkori-Ghanbaria A, Waller MJ, Weston P, Widaa S, Whittaker P, Barroso I, Deloukas P, Mathew CG, Blackwell JM, Brown MA, Corvin AP, McCarthy MI, Spencer CC, Bramon E, Corvin AP, O'Donovan MC, Stefansson K, Scolnick E, Purcell S, McCarroll SA, Sklar P, Hultman CM, Sullivan PF (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 45 (10):1150-1159. doi:10.1038/ng.2742

  34. Siegert S, Seo J, Kwon EJ, Rudenko A, Cho S, Wang WY, Flood Z, Martorell AJ, Ericsson M, Mungenast AE, Tsai LH (2015) The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nat Neurosci 18(7):1008. https://doi.org/10.1038/nn.4023

    Article  CAS  Google Scholar 

  35. Feingold M, Hall BD, Lacassie Y, Martinez-Frias ML (1997) Syndrome of microcephaly, facial and hand abnormalities, tracheoesophageal fistula, duodenal atresia, and developmental delay. Am J Med Genet 69(3):245–249

    Article  CAS  Google Scholar 

  36. de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, Van Haeringen A, Genevieve D, Goldenberg A, Oufadem M, Manouvrier S, Munnich A, Vidigal JA, Vekemans M, Lyonnet S, Henrion-Caude A, Ventura A, Amiel J (2011) Germline deletion of the miR-17 approximately 92 cluster causes skeletal and growth defects in humans. Nat Genet 43(10):1026–1030. https://doi.org/10.1038/ng.915

    Article  CAS  Google Scholar 

  37. Pan WL, Chopp M, Fan B, Zhang R, Wang X, Hu J, Zhang XM, Zhang ZG, Liu XS (2019) Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function. FASEB J 33(4):5257–5267. https://doi.org/10.1096/fj.201801019R

    Article  CAS  Google Scholar 

  38. Jin J, Kim SN, Liu X, Zhang H, Zhang C, Seo JS, Kim Y, Sun T (2016) miR-17-92 cluster regulates adult hippocampal neurogenesis, anxiety, and depression. Cell Rep 16(6):1653–1663. https://doi.org/10.1016/j.celrep.2016.06.101

    Article  CAS  Google Scholar 

  39. Fiori E, Babicola L, Andolina D, Coassin A, Pascucci T, Patella L, Han YC, Ventura A, Ventura R (2015) Neurobehavioral alterations in a genetic murine model of Feingold Syndrome 2. Behav Genet 45(5):547–559. https://doi.org/10.1007/s10519-015-9724-8

    Article  CAS  Google Scholar 

  40. Toma C, Torrico B, Hervas A, Salgado M, Rueda I, Valdes-Mas R, Buitelaar JK, Rommelse N, Franke B, Freitag C, Reif A, Perez-Jurado LA, Battaglia A, Mazzone L, Bacchelli E, Puente XS, Cormand B (2015) Common and rare variants of microRNA genes in autism spectrum disorders. World J Biol Psychiatry 16(6):376–386. https://doi.org/10.3109/15622975.2015.1029518

    Article  Google Scholar 

  41. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, Mahajan M, Manaa D, Pawitan Y, Reichert J, Ripke S, Sandin S, Sklar P, Svantesson O, Reichenberg A, Hultman CM, Devlin B, Roeder K, Buxbaum JD (2014) Most genetic risk for autism resides with common variation. Nat Genet 46(8):881–885. https://doi.org/10.1038/ng.3039

    Article  CAS  Google Scholar 

  42. Huguet G, Ey E, Bourgeron T (2013) The genetic landscapes of autism spectrum disorders. Annu Rev Genomics Hum Genet 14:191–213. https://doi.org/10.1146/annurev-genom-091212-153431

    Article  CAS  Google Scholar 

  43. Basu SN, Kollu R, Banerjee-Basu S (2009) AutDB: a gene reference resource for autism research. Nucleic Acids Res 37(Database issue):D832–836. https://doi.org/10.1093/nar/gkn835

    Article  CAS  Google Scholar 

  44. Mazzio EA, Soliman KF (2012) Basic concepts of epigenetics: impact of environmental signals on gene expression. Epigenetics 7(2):119–130. https://doi.org/10.4161/epi.7.2.18764

    Article  CAS  Google Scholar 

  45. Abu-Elneel K, Liu T, Gazzaniga FS, Nishimura Y, Wall DP, Geschwind DH, Lao K, Kosik KS (2008) Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics 9(3):153–161. https://doi.org/10.1007/s10048-008-0133-5

    Article  CAS  Google Scholar 

  46. Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM (2015) Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders. Mol Autism 6:37. https://doi.org/10.1186/s13229-015-0029-9

    Article  CAS  Google Scholar 

  47. Stamova B, Ander BP, Barger N, Sharp FR, Schumann CM (2015) Specific regional and age-related small noncoding RNA expression patterns within superior temporal gyrus of typical human brains are less distinct in autism brains. J Child Neurol 30(14):1930–1946. https://doi.org/10.1177/0883073815602067

    Article  Google Scholar 

  48. Mor M, Nardone S, Sams DS, Elliott E (2015) Hypomethylation of miR-142 promoter and upregulation of microRNAs that target the oxytocin receptor gene in the autism prefrontal cortex. Mol Autism 6:46. https://doi.org/10.1186/s13229-015-0040-1

    Article  CAS  Google Scholar 

  49. Huang F, Long Z, Chen Z, Li J, Hu Z, Qiu R, Zhuang W, Tang B, Xia K, Jiang H (2015) Investigation of gene regulatory networks associated with autism spectrum disorder based on MiRNA expression in China. PLoS ONE 10(6):e0129052. https://doi.org/10.1371/journal.pone.0129052

    Article  CAS  Google Scholar 

  50. Mundalil Vasu M, Anitha A, Thanseem I, Suzuki K, Yamada K, Takahashi T, Wakuda T, Iwata K, Tsujii M, Sugiyama T, Mori N (2014) Serum microRNA profiles in children with autism. Mol Autism 5:40. https://doi.org/10.1186/2040-2392-5-40

    Article  CAS  Google Scholar 

  51. Ghahramani Seno MM, Hu P, Gwadry FG, Pinto D, Marshall CR, Casallo G, Scherer SW (2011) Gene and miRNA expression profiles in autism spectrum disorders. Brain Res 1380:85–97. https://doi.org/10.1016/j.brainres.2010.09.046

    Article  CAS  Google Scholar 

  52. Sarachana T, Zhou R, Chen G, Manji HK, Hu VW (2010) Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines. Genome Med 2(4):23. https://doi.org/10.1186/gm144

    Article  CAS  Google Scholar 

  53. Talebizadeh Z, Butler MG, Theodoro MF (2008) Feasibility and relevance of examining lymphoblastoid cell lines to study role of microRNAs in autism. Autism Res 1(4):240–250. https://doi.org/10.1002/aur.33

    Article  Google Scholar 

  54. Nguyen LS, Lepleux M, Makhlouf M, Martin C, Fregeac J, Siquier-Pernet K, Philippe A, Feron F, Gepner B, Rougeulle C, Humeau Y, Colleaux L (2016) Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology. Mol Autism 7:1. https://doi.org/10.1186/s13229-015-0064-6

    Article  CAS  Google Scholar 

  55. Ziats MN, Rennert OM (2014) Identification of differentially expressed microRNAs across the developing human brain. Mol Psychiatry 19(7):848–852. https://doi.org/10.1038/mp.2013.93

    Article  CAS  Google Scholar 

  56. Yu D, Jiao XQ, Cao T, Huang FS (2018) Serum miRNA expression profiling reveals miR-486-3p may play a significant role in the development of autism by targeting ARID1B. NeuroReport 29(17):1431–1436. https://doi.org/10.1097/Wnr.0000000000001107

    Article  CAS  Google Scholar 

  57. Hicks SD, Carpenter RL, Wagner KE, Pauley R, Barros M, Tierney-Aves C, Barns S, Greene CD, Middleton FA (2020) Saliva MicroRNA differentiates children with autism from peers with typical and atypical development. J Am Acad Child Adolesc Psychiatry 59(2):296–308. https://doi.org/10.1016/j.jaac.2019.03.017

    Article  Google Scholar 

  58. Jovicic A, Roshan R, Moisoi N, Pradervand S, Moser R, Pillai B, Luthi-Carter R (2013) Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J Neurosci 33(12):5127–5137. https://doi.org/10.1523/JNEUROSCI.0600-12.2013

    Article  CAS  Google Scholar 

  59. Nguyen LS, Fregeac J, Bole-Feysot C, Cagnard N, Iyer A, Anink J, Aronica E, Alibeu O, Nitschke P, Colleaux L (2018) Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders. Mol Autism 9:38. https://doi.org/10.1186/s13229-018-0219-3

    Article  CAS  Google Scholar 

  60. Chen YL, Shen CK (2013) Modulation of mGluR-dependent MAP1B translation and AMPA receptor endocytosis by microRNA miR-146a-5p. J Neurosci 33(21):9013–9020. https://doi.org/10.1523/JNEUROSCI.5210-12.2013

    Article  CAS  Google Scholar 

  61. Hicks SD, Rajan AT, Wagner KE, Barns S, Carpenter RL, Middleton FA (2018) Validation of a salivary RNA test for childhood autism spectrum disorder. Front Genet 9:534. https://doi.org/10.3389/fgene.2018.00534

    Article  CAS  Google Scholar 

  62. Aronica E, Fluiter K, Iyer A, Zurolo E, Vreijling J, van Vliet EA, Baayen JC, Gorter JA (2010) Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy. Eur J Neurosci 31(6):1100–1107. https://doi.org/10.1111/j.1460-9568.2010.07122.x

    Article  CAS  Google Scholar 

  63. Iyer A, Zurolo E, Prabowo A, Fluiter K, Spliet WG, van Rijen PC, Gorter JA, Aronica E (2012) MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response. PLoS ONE 7(9):e44789. https://doi.org/10.1371/journal.pone.0044789

    Article  CAS  Google Scholar 

  64. Hsu PK, Xu B, Mukai J, Karayiorgou M, Gogos JA (2015) The BDNF Val66Met variant affects gene expression through miR-146b. Neurobiol Dis 77:228–237. https://doi.org/10.1016/j.nbd.2015.03.004

    Article  CAS  Google Scholar 

  65. Guo Q, Zhang J, Li J, Zou L, Zhang J, Xie Z, Fu X, Jiang S, Chen G, Jia Q, Li F, Wan Y, Wu Y (2013) Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells. Blood 121(24):4875–4883. https://doi.org/10.1182/blood-2012-08-452425

    Article  CAS  Google Scholar 

  66. Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley PS, Baltimore D (2011) miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 208(6):1189–1201. https://doi.org/10.1084/jem.20101823

    Article  CAS  Google Scholar 

  67. Hannenhalli S, Kaestner KH (2009) The evolution of Fox genes and their role in development and disease. Nat Rev Genet 10(4):233–240. https://doi.org/10.1038/nrg2523

    Article  CAS  Google Scholar 

  68. Clovis YM, Enard W, Marinaro F, Huttner WB, De Pietri TD (2012) Convergent repression of Foxp2 3'UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons. Development 139(18):3332–3342. https://doi.org/10.1242/dev.078063

    Article  CAS  Google Scholar 

  69. Tognini P, Putignano E, Coatti A, Pizzorusso T (2011) Experience-dependent expression of miR-132 regulates ocular dominance plasticity. Nat Neurosci 14(10):1237–1239. https://doi.org/10.1038/nn.2920

    Article  CAS  Google Scholar 

  70. Hansen KF, Sakamoto K, Wayman GA, Impey S, Obrietan K (2010) Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory. PLoS ONE 5(11):e15497. https://doi.org/10.1371/journal.pone.0015497

    Article  CAS  Google Scholar 

  71. Cheng TL, Qiu Z (2014) MeCP2: multifaceted roles in gene regulation and neural development. Neurosci Bull 30(4):601–609. https://doi.org/10.1007/s12264-014-1452-6

    Article  CAS  Google Scholar 

  72. Cheng TL, Wang Z, Liao Q, Zhu Y, Zhou WH, Xu W, Qiu Z (2014) MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Dev Cell 28(5):547–560. https://doi.org/10.1016/j.devcel.2014.01.032

    Article  CAS  Google Scholar 

  73. Lyu JW, Yuan B, Cheng TL, Qiu ZL, Zhou WH (2016) Reciprocal regulation of autism-related genes MeCP2 and PTEN via microRNAs. Sci Rep 6:20392. https://doi.org/10.1038/srep20392

    Article  CAS  Google Scholar 

  74. Han K, Gennarino VA, Lee Y, Pang K, Hashimoto-Torii K, Choufani S, Raju CS, Oldham MC, Weksberg R, Rakic P, Liu Z, Zoghbi HY (2013) Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes Dev 27(5):485–490. https://doi.org/10.1101/gad.207456.112

    Article  CAS  Google Scholar 

  75. Jacquemont ML, Sanlaville D, Redon R, Raoul O, Cormier-Daire V, Lyonnet S, Amiel J, Le Merrer M, Heron D, de Blois MC, Prieur M, Vekemans M, Carter NP, Munnich A, Colleaux L, Philippe A (2006) Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet 43(11):843–849. https://doi.org/10.1136/jmg.2006.043166

    Article  CAS  Google Scholar 

  76. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M (2007) Strong association of de novo copy number mutations with autism. Science 316(5823):445–449. https://doi.org/10.1126/science.1138659

    Article  CAS  Google Scholar 

  77. Marrale M, Albanese NN, Cali F, Romano V (2014) Assessing the impact of copy number variants on miRNA genes in autism by Monte Carlo simulation. PLoS ONE 9(3):e90947. https://doi.org/10.1371/journal.pone.0090947

    Article  CAS  Google Scholar 

  78. Iwai N, Naraba H (2005) Polymorphisms in human pre-miRNAs. Biochem Biophys Res Commun 331(4):1439–1444. https://doi.org/10.1016/j.bbrc.2005.04.051

    Article  CAS  Google Scholar 

  79. Saunders MA, Liang H, Li WH (2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA 104(9):3300–3305. https://doi.org/10.1073/pnas.0611347104

    Article  CAS  Google Scholar 

  80. Li L, Meng T, Jia Z, Zhu G, Shi B (2010) Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. Am J Med Genet A 152A(4):856–862. https://doi.org/10.1002/ajmg.a.33236

    Article  CAS  Google Scholar 

  81. Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ (2009) SNPs in human miRNA genes affect biogenesis and function. RNA 15(9):1640–1651. https://doi.org/10.1261/rna.1560209

    Article  CAS  Google Scholar 

  82. Dietert RR, Dietert JM, Dewitt JC (2011) Environmental risk factors for autism. Emerg Health Threats J 4:7111. https://doi.org/10.3402/ehtj.v4i0.7111

    Article  Google Scholar 

  83. Lancon A, Michaille JJ, Latruffe N (2013) Effects of dietary phytophenols on the expression of microRNAs involved in mammalian cell homeostasis. J Sci Food Agric 93(13):3155–3164. https://doi.org/10.1002/jsfa.6228

    Article  CAS  Google Scholar 

  84. Li Y, Kong D, Wang Z, Sarkar FH (2010) Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm Res 27(6):1027–1041. https://doi.org/10.1007/s11095-010-0105-y

    Article  CAS  Google Scholar 

  85. Weldon BA, Shubin SP, Smith MN, Workman T, Artemenko A, Griffith WC, Thompson B, Faustman EM (2016) Urinary microRNAs as potential biomarkers of pesticide exposure. Toxicol Appl Pharmacol 312:19–25. https://doi.org/10.1016/j.taap.2016.01.018

    Article  CAS  Google Scholar 

  86. Venault P, Chapouthier G (2007) Plasticity and anxiety. Neural Plast 2007:75617. https://doi.org/10.1155/2007/75617

    Article  Google Scholar 

  87. Osuch EA, Ketter TA, Kimbrell TA, George MS, Benson BE, Willis MW, Herscovitch P, Post RM (2000) Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients. Biol Psychiatry 48(10):1020–1023. https://doi.org/10.1016/s0006-3223(00)00920-3

    Article  CAS  Google Scholar 

  88. Davidson RJ, Abercrombie H, Nitschke JB, Putnam K (1999) Regional brain function, emotion and disorders of emotion. Curr Opin Neurobiol 9(2):228–234

    Article  CAS  Google Scholar 

  89. McNaughton N (1997) Cognitive dysfunction resulting from hippocampal hyperactivity—a possible cause of anxiety disorder? Pharmacol Biochem Behav 56(4):603–611. https://doi.org/10.1016/s0091-3057(96)00419-4

    Article  CAS  Google Scholar 

  90. Haramati S, Navon I, Issler O, Ezra-Nevo G, Gil S, Zwang R, Hornstein E, Chen A (2011) MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. J Neurosci 31(40):14191–14203. https://doi.org/10.1523/JNEUROSCI.1673-11.2011

    Article  CAS  Google Scholar 

  91. Andolina D, Di Segni M, Bisicchia E, D'Alessandro F, Cestari V, Ventura A, Concepcion C, Puglisi-Allegra S, Ventura R (2016) Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety. Neuropharmacology 107:305–316. https://doi.org/10.1016/j.neuropharm.2016.03.044

    Article  CAS  Google Scholar 

  92. Zhu J, Chen Z, Tian J, Meng Z, Ju M, Wu G, Tian Z (2017) miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1. Int J Mol Med 40(1):90–100. https://doi.org/10.3892/ijmm.2017.2981

    Article  CAS  Google Scholar 

  93. Aten S, Page CE, Kalidindi A, Wheaton K, Niraula A, Godbout JP, Hoyt KR, Obrietan K (2019) miR-132/212 is induced by stress and its dysregulation triggers anxiety-related behavior. Neuropharmacology 144:256–270. https://doi.org/10.1016/j.neuropharm.2018.10.020

    Article  CAS  Google Scholar 

  94. Cohen JL, Jackson NL, Ballestas ME, Webb WM, Lubin FD, Clinton SM (2017) Amygdalar expression of the microRNA miR-101a and its target Ezh2 contribute to rodent anxiety-like behaviour. Eur J Neurosci 46(7):2241–2252. https://doi.org/10.1111/ejn.13624

    Article  Google Scholar 

  95. Fonken LK, Gaudet AD, Gaier KR, Nelson RJ, Popovich PG (2016) MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice. Psychoneuroendocrinology 63:362–369. https://doi.org/10.1016/j.psyneuen.2015.10.019

    Article  CAS  Google Scholar 

  96. Issler O, Haramati S, Paul ED, Maeno H, Navon I, Zwang R, Gil S, Mayberg HS, Dunlop BW, Menke A, Awatramani R, Binder EB, Deneris ES, Lowry CA, Chen A (2014) MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron 83(2):344–360. https://doi.org/10.1016/j.neuron.2014.05.042

    Article  CAS  Google Scholar 

  97. Mannironi C, Biundo A, Rajendran S, De Vito F, Saba L, Caioli S, Zona C, Ciotti T, Caristi S, Perlas E, Del Vecchio G, Bozzoni I, Rinaldi A, Mele A, Presutti C (2018) miR-135a regulates synaptic transmission and anxiety-like behavior in amygdala. Mol Neurobiol 55(4):3301–3315. https://doi.org/10.1007/s12035-017-0564-9

    Article  CAS  Google Scholar 

  98. Marty V, Labialle S, Bortolin-Cavaille ML, Ferreira De Medeiros G, Moisan MP, Florian C, Cavaille J (2016) Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus enhances anxiety-related behaviour. Hum Mol Genet 25(4):728–739. https://doi.org/10.1093/hmg/ddv510

    Article  CAS  Google Scholar 

  99. Parsons MJ, Grimm CH, Paya-Cano JL, Sugden K, Nietfeld W, Lehrach H, Schalkwyk LC (2008) Using hippocampal microRNA expression differences between mouse inbred strains to characterise miRNA function. Mamm Genome 19(7–8):552–560. https://doi.org/10.1007/s00335-008-9116-y

    Article  CAS  Google Scholar 

  100. Rinaldi A, Vincenti S, De Vito F, Bozzoni I, Oliverio A, Presutti C, Fragapane P, Mele A (2010) Stress induces region specific alterations in microRNAs expression in mice. Behav Brain Res 208(1):265–269. https://doi.org/10.1016/j.bbr.2009.11.012

    Article  CAS  Google Scholar 

  101. Uchida S, Nishida A, Hara K, Kamemoto T, Suetsugi M, Fujimoto M, Watanuki T, Wakabayashi Y, Otsuki K, McEwen BS, Watanabe Y (2008) Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor. Eur J Neurosci 27(9):2250–2261. https://doi.org/10.1111/j.1460-9568.2008.06218.x

    Article  Google Scholar 

  102. Babenko O, Golubov A, Ilnytskyy Y, Kovalchuk I, Metz GA (2012) Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming. PLoS ONE 7(1):e29441. https://doi.org/10.1371/journal.pone.0029441

    Article  CAS  Google Scholar 

  103. Bradesi S, Karagiannides I, Bakirtzi K, Joshi SM, Koukos G, Iliopoulos D, Pothoulakis C, Mayer EA (2015) Identification of spinal cord microRNA and gene signatures in a model of chronic stress-induced visceral hyperalgesia in rat. PLoS ONE 10(7):e0130938. https://doi.org/10.1371/journal.pone.0130938

    Article  CAS  Google Scholar 

  104. Zhang Y, Wang Y, Wang L, Bai M, Zhang X, Zhu X (2015) Dopamine receptor D2 and associated microRNAs are involved in stress susceptibility and resistance to escitalopram treatment. Int J Neuropsychopharmacol. https://doi.org/10.1093/ijnp/pyv025

    Article  Google Scholar 

  105. Meerson A, Cacheaux L, Goosens KA, Sapolsky RM, Soreq H, Kaufer D (2010) Changes in brain MicroRNAs contribute to cholinergic stress reactions. J Mol Neurosci 40(1–2):47–55. https://doi.org/10.1007/s12031-009-9252-1

    Article  CAS  Google Scholar 

  106. Nadorp B, Soreq H (2014) Predicted overlapping microRNA regulators of acetylcholine packaging and degradation in neuroinflammation-related disorders. Front Mol Neurosci 7:9. https://doi.org/10.3389/fnmol.2014.00009

    Article  CAS  Google Scholar 

  107. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17(5):667–669. https://doi.org/10.1038/nn.3695

    Article  CAS  Google Scholar 

  108. Gapp K, van Steenwyk G, Germain PL, Matsushima W, Rudolph KLM, Manuella F, Roszkowski M, Vernaz G, Ghosh T, Pelczar P, Mansuy IM, Miska EA (2018) Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0271-6

    Article  Google Scholar 

  109. Benaroya-Milshtein N, Hollander N, Apter A, Kukulansky T, Raz N, Wilf A, Yaniv I, Pick CG (2004) Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity. Eur J Neurosci 20(5):1341–1347. https://doi.org/10.1111/j.1460-9568.2004.03587.x

    Article  CAS  Google Scholar 

  110. Brenes JC, Lackinger M, Hoglinger GU, Schratt G, Schwarting RK, Wohr M (2016) Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J Comp Neurol 524(8):1586–1607. https://doi.org/10.1002/cne.23842

    Article  CAS  Google Scholar 

  111. Hohoff C, Weber H, Richter J, Domschke K, Zwanzger PM, Ohrmann P, Bauer J, Suslow T, Kugel H, Baumann C, Klauke B, Jacob CP, Fritze J, Bandelow B, Gloster AT, Gerlach AL, Kircher T, Lang T, Alpers GW, Strohle A, Fehm L, Wittchen HU, Arolt V, Pauli P, Hamm A, Reif A, Deckert J (2015) RGS2 genetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety. Am J Med Genet B Neuropsychiatr Genet 168B(3):211–222. https://doi.org/10.1002/ajmg.b.32299

    Article  CAS  Google Scholar 

  112. Leygraf A, Hohoff C, Freitag C, Willis-Owen SA, Krakowitzky P, Fritze J, Franke P, Bandelow B, Fimmers R, Flint J, Deckert J (2006) Rgs 2 gene polymorphisms as modulators of anxiety in humans? J Neural Transm (Vienna) 113(12):1921–1925. https://doi.org/10.1007/s00702-006-0484-8

    Article  CAS  Google Scholar 

  113. Hommers L, Raab A, Bohl A, Weber H, Scholz CJ, Erhardt A, Binder E, Arolt V, Gerlach A, Gloster A, Kalisch R, Kircher T, Lonsdorf T, Strohle A, Zwanzger P, Mattheisen M, Cichon S, Lesch KP, Domschke K, Reif A, Lohse MJ, Deckert J (2015) MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits. Am J Med Genet B Neuropsychiatr Genet 168B(4):296–306. https://doi.org/10.1002/ajmg.b.32312

    Article  CAS  Google Scholar 

  114. Muinos-Gimeno M, Espinosa-Parrilla Y, Guidi M, Kagerbauer B, Sipila T, Maron E, Pettai K, Kananen L, Navines R, Martin-Santos R, Gratacos M, Metspalu A, Hovatta I, Estivill X (2011) 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 69(6):526–533. https://doi.org/10.1016/j.biopsych.2010.10.010

    Article  CAS  Google Scholar 

  115. Wang X, Sundquist K, Hedelius A, Palmer K, Memon AA, Sundquist J (2015) Circulating microRNA-144-5p is associated with depressive disorders. Clin Epigenet 7:69. https://doi.org/10.1186/s13148-015-0099-8

    Article  CAS  Google Scholar 

  116. Rajman M, Schratt G (2017) MicroRNAs in neural development: from master regulators to fine-tuners. Development 144(13):2310–2322. https://doi.org/10.1242/dev.144337

    Article  CAS  Google Scholar 

  117. Issler O, Chen A (2015) Determining the role of microRNAs in psychiatric disorders. Nat Rev Neurosci 16(4):201–212. https://doi.org/10.1038/nrn3879

    Article  CAS  Google Scholar 

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Acknowledgements

We apologize to colleagues whose work we were not able to discuss due to space limitations. Work in the Schratt laboratory is in part funded by grants from the Swiss National Science Foundation (SNSF; 310030E_179651, 32NE30_189486), Deutsche Forschungsgemeinschaft (DFG; FI 2157/2-1, DI 1501/5-2) and ETH Zurich Marie Curie COFUND postdoc fellowship to R. Narayanan.

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Narayanan, R., Schratt, G. miRNA regulation of social and anxiety-related behaviour. Cell. Mol. Life Sci. 77, 4347–4364 (2020). https://doi.org/10.1007/s00018-020-03542-7

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