Effects of Aberrant MiR-384-5p Expression on Learning and Memory in a Rat Model of Attention Deficit Hyperactivity Disorder

Overview

Journal Front Neurol

Specialty Neurology

Date 2020 Mar 3

PMID 32116987

Citations 7

Authors

Qu Xu

Jiaxin Ou

Qingyu Zhang

Ranran Tang

Jing Wang

Qin Hong

Xirong Guo

Meiling Tong

Lei Yang

Xia Chi

Affiliations

Soon will be listed here.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder characterized by inattention, hyperactivity, and impulsivity. It may be accompanied by learning difficulties and working memory deficits. Few studies have examined the role of miRNAs in cognitive dysfunction in ADHD. This study investigated the effects of aberrant miR-384-5p expression on learning and memory in a widely used ADHD rat model. Lentiviral vectors were injected into the lateral ventricles of the rats to increase or decrease miR-384-5p level. To determine whether aberrant miR-384-5p expression affects learning and memory, spontaneous activity and cognitive function were assessed with the open field and Morris water maze tests. In the place navigation experiment of the Morris water maze test, time, and total swimming distance to reach the platform decreased compared to the control group when miR-384-5p was overexpressed, whereas down-regulation of miR-384-5p had the opposite effect. There were no obvious changes in brain tissue morphology following miR-384-5p overexpression or inhibition; however, dopamine (DA) receptor D1 (DRD1) level has decreased and increased, respectively, in the prefrontal cortex (PFC). The luciferase activity of the wild-type DRD1 group has decreased in luciferase reporter assay. Cyclic AMP response element-binding protein (CREB) phosphorylation has increased, and DA transporter (DAT) level has decreased in the PFC of spontaneously hypertensive rats (SHR) by miR-384-5p overexpression. On the other hand, miR-384-5p suppression increased DRD1 and decreased DAT and CREB protein levels relative to control rats. These findings suggest that miR-384-5p may play a critical role in learning and memory impairment in ADHD.

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References

Whitaker C, Wei H . An alternate cAMP pathway Epac promotes hippocampal long-term depression. J Physiol. 2009; 587(Pt 13):3067-8. PMC: 2727013. DOI: 10.1113/jphysiol.2009.175216. View

Gomez A, Midde N, Mactutus C, Booze R, Zhu J . Environmental enrichment alters nicotine-mediated locomotor sensitization and phosphorylation of DARPP-32 and CREB in rat prefrontal cortex. PLoS One. 2012; 7(8):e44149. PMC: 3432100. DOI: 10.1371/journal.pone.0044149. View

Kandemir H, Erdal M, Selek S, Ay O, Karababa I, Kandemir S . Evaluation of several micro RNA (miRNA) levels in children and adolescents with attention deficit hyperactivity disorder. Neurosci Lett. 2014; 580:158-62. DOI: 10.1016/j.neulet.2014.07.060. View

Jichao S, Xinmin H, Xianguo R, Dongqi Y, Rongyi Z, Shuang L . Saikosaponin A Alleviates Symptoms of Attention Deficit Hyperactivity Disorder through Downregulation of DAT and Enhancing BDNF Expression in Spontaneous Hypertensive Rats. Evid Based Complement Alternat Med. 2017; 2017:2695903. PMC: 5331296. DOI: 10.1155/2017/2695903. View

Rizzo R, Ragusa M, Barbagallo C, Sammito M, Gulisano M, Cali P . Circulating miRNAs profiles in Tourette syndrome: molecular data and clinical implications. Mol Brain. 2015; 8:44. PMC: 4513635. DOI: 10.1186/s13041-015-0133-y. View

Capitano F, Camon J, Licursi V, Ferretti V, Maggi L, Scianni M . MicroRNA-335-5p modulates spatial memory and hippocampal synaptic plasticity. Neurobiol Learn Mem. 2017; 139:63-68. DOI: 10.1016/j.nlm.2016.12.019. View

Wu Y, Parikshak N, Belgard T, Geschwind D . Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder. Nat Neurosci. 2016; 19(11):1463-1476. PMC: 5841760. DOI: 10.1038/nn.4373. View

Sanchez-Mora C, Ramos-Quiroga J, Bosch R, Corrales M, Garcia-Martinez I, Nogueira M . Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene for the disorder. Neuropsychopharmacology. 2014; 40(4):915-26. PMC: 4330505. DOI: 10.1038/npp.2014.267. View

Alural B, Genc S, Haggarty S . Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 73:87-103. PMC: 5292013. DOI: 10.1016/j.pnpbp.2016.03.010. View

10.

Srivastav S, Walitza S, Grunblatt E . Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic review. Atten Defic Hyperact Disord. 2017; 10(1):49-63. DOI: 10.1007/s12402-017-0232-y. View

11.

Smiley J, Levey A, Ciliax B, Goldman-Rakic P . D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines. Proc Natl Acad Sci U S A. 1994; 91(12):5720-4. PMC: 44068. DOI: 10.1073/pnas.91.12.5720. View

12.

Davids E, Zhang K, Tarazi F, Baldessarini R . Animal models of attention-deficit hyperactivity disorder. Brain Res Brain Res Rev. 2003; 42(1):1-21. DOI: 10.1016/s0165-0173(02)00274-6. View

13.

Geaghan M, Cairns M . MicroRNA and Posttranscriptional Dysregulation in Psychiatry. Biol Psychiatry. 2015; 78(4):231-9. DOI: 10.1016/j.biopsych.2014.12.009. View

14.

Banaschewski T, Becker K, Scherag S, Franke B, Coghill D . Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry. 2010; 19(3):237-57. PMC: 2839490. DOI: 10.1007/s00787-010-0090-z. View

15.

Swanson J, Kinsbourne M, Nigg J, Lanphear B, Stefanatos G, Volkow N . Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev. 2007; 17(1):39-59. DOI: 10.1007/s11065-007-9019-9. View

16.

Vorhees C, Williams M . Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2007; 1(2):848-58. PMC: 2895266. DOI: 10.1038/nprot.2006.116. View

17.

Wang C, Niu M, Zhou Z, Zheng X, Zhang L, Tian Y . VPS35 regulates cell surface recycling and signaling of dopamine receptor D1. Neurobiol Aging. 2016; 46:22-31. PMC: 5018432. DOI: 10.1016/j.neurobiolaging.2016.05.016. View

18.

Jackson D, Westlind-Danielsson A . Dopamine receptors: molecular biology, biochemistry and behavioural aspects. Pharmacol Ther. 1994; 64(2):291-370. DOI: 10.1016/0163-7258(94)90041-8. View

19.

Sergeant J . The cognitive-energetic model: an empirical approach to attention-deficit hyperactivity disorder. Neurosci Biobehav Rev. 2000; 24(1):7-12. DOI: 10.1016/s0149-7634(99)00060-3. View

20.

Garcia-Martinez I, Sanchez-Mora C, Pagerols M, Richarte V, Corrales M, Fadeuilhe C . Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder. Transl Psychiatry. 2016; 6(8):e879. PMC: 5022091. DOI: 10.1038/tp.2016.151. View