BELLEĞİN EPİGENETİK DÜZENLENMESİ: MİKRORNA’LARIN ROLÜ
Year 2018,
Volume: 27 Issue: 1, 87 - 94, 01.03.2018
Sebahattin Karabulut
Keziban Korkmaz Bayramov
Asuman Gölgeli
Abstract
“MikroRNA(miRNA)’lar” kodlanmayan RNA’lar sınıfına
ait moleküller olup, protein sentezinin transkripsiyon
sonrası (posttranskripsiyonel) düzenleyicileri olarak
tanımlanırlar. Bu posttranskripsiyonel düzenlemenin
neredeyse tüm biyolojik süreçlerde rol oynadığı düşünülmektedir. Son zamanlarda miRNA aracılı bu regülasyonun, aktivite bağımlı gen ekspresyonunun yer aldığı
öğrenme ve bellek oluşumu için de kritik olduğu anlaşılmıştır. Bu endojen RNA’ların sadece öğrenme ve bellek
gibi normal beyin fonksiyonlarında değil, aynı zamanda
bilişsel işlevlerin etkilendiği çok sayıda nörodejeneratif
hastalığın fizyopatolojisinde de işe karıştığı gösterilmiştir. Bu derlemede miRNA’ların sinaptik plastisitedeki
rolleri ve bazı nörodejeneratif hastalıklarla ilişkileri ele
alınmıştır. Nöral plastisitede miRNA’ların rollerinin tam
olarak anlaşılması, bellek fonksiyonlarının bozulduğu
nörolojik hastalıklar için genetik tedavilerin ve yeni
teşhis yöntemlerinin gelişimine kapı açabilecektir.”
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The Epıgenetıc Regulatıon Of Memory: The Role Of Mıcrornas
Year 2018,
Volume: 27 Issue: 1, 87 - 94, 01.03.2018
Sebahattin Karabulut
Keziban Korkmaz Bayramov
Asuman Gölgeli
Abstract
“MicroRNAs (miRNAs)” are a class of non-coding RNAs
defined as posttranscriptional regulators of protein
synthesis. It is believed that this posttranscriptional
regulation has been implicated in virtually all aspects
of biological processes. Recently, it has been understood that miRNA-mediated regulation is critical for
learning and memory formation which requires activity-dependent gene expression. Emerging evidence
indicates that these endogenous RNAs are involved in
not only normal brain functions such as learning and
memory, but also the pathophysiology of many neurodegenerative diseases in which cognitive functions
are influenced. In this review, the roles of miRNAs in
synaptic plasticity and their relation to some neurodegenerative diseases are discussed. With further elaboration of the role of miRNAs in neural plasticity, the
door will be opened for the development of new diagnostic tests and genetic therapies for neurodegenerative diseases in which memory functions are impaired.”
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microRNA regulates neuronal morphogenesis. Proc
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down-regulating p250GAP. Proc Natl Acad Sci
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Neuronal activity rapidly induces transcription of
the CREB-regulated microRNA-132, in vivo.
Hippocampus 2010; 20:492-498.
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experience-dependent microRNA, is essential for
visual cortex plasticity. Nat Neurosci 2011;
14:1240-1242.
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Brain Struct Funct 2013; 218:817-831.
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miRNA Expression profile after status epilepticus
and hippocampal neuroprotection by targeting miR
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hippocampal synaptogenesis via CREB-regulated
microRNA-132 suppression of p250GAP. Mol
Endocrinol 2014; 28:1073-1087.
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the nervous system. Cell Res 2005; 15:255-261.
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function. Biochem Cell Biol 2011; 89:1-11
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formation and retention are affected in adult miR132/212 knockout mice. Behav Brain Res 2015;
287:15-26.
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deletion of miR-132/-212 impairs memory and
alters the hippocampal transcriptome. Learn Mem
2016; 23:61-71.
- 32. Jasińska M, Miłek J, Cymerman IA, Łęski S,
Kaczmarek L, Dziembowska M. miR-132 Regulates
Dendritic Spine Structure by Direct Targeting of
Matrix Metalloproteinase 9 mRNA. Mol Neurobiol
2016; 53:4701-4712.
- 33. Eacker SM, Keuss MJ, Berezikov E, Dawson VL,
Dawson TM. Neuronal activity regulates
hippocampal miRNA expression. PloS One 2011;
6:e25068.
- 34. Åkerblom M, Sachdeva R, Barde I, et al. MicroRNA124 is a subventricular zone neuronal fate determinant. J Neurosci 2012; 32:8879-8889.
- 35. Rajasethupathy P, Fiumara F, Sheridan R, et al.
Characterization of small RNAs in Aplysia reveals a
role for miR-124 in constraining synaptic plasticity
through CREB. Neuron 2009; 63:803-817.
- 36. Yang Y, Shu X, Liu D, et al. EPAC null mutation
impairs learning and social interactions via
aberrant regulation of miR-124 and Zif268
translation. Neuron 2012; 73:774-788.
- 37. Motti D, Bixby JL, Lemmon VP. MicroRNAs and
neuronal development. Semin Fetal Neonatal Med
2012; 17:347-352.
- 38. Giusti SA, Vogl AM, Brockmann MM, et al.
MicroRNA-9 controls dendritic development by
targeting REST. eLife 2014; 3:1-22.
- 39. Sim SE, Lim CS, Kim JI, et al. The Brain-Enriched
MicroRNA miR-9-3p Regulates Synaptic Plasticity
and Memory. J Neurosci 2016; 36:8641-8652.
- 40. Malmevik J, Petri R, Knauff P, et al. Distinct
cognitive effects and underlying transcriptome
changes upon inhibition of individual miRNAs in
hippocampal neurons. Scientific Reports 2016; 6:1-
14.
- 41. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini
ME, Kiebler M, Greenberg ME. A brain-specific
microRNA regulates dendritic spine development.
Nature 2006; 439: 283-289.
- 42. Siegel G, Obernosterer G, Fiore R, et al. A functional
screen implicates microRNA-138-dependent
regulation of the depalmitoylation enzyme APT1 in
dendritic spine morphogenesis. Nat Cell Biol 2009;
11:705-716.
- 43. Griggs EM, Young EJ, Rumbaugh G, Miller CA.
MicroRNA-182 regulates amygdala-dependent
memory formation. J Neurosci 2013; 33:1734-
1740.
- 44. Woldemichael BT, Jawaid A, Kremer EA, et al. The
microRNA cluster miR-183/96/182 contributes to
long-term memory in a protein phosphatase 1-
dependent manner. Nat Commun 2016; 25:12594.
- 45. Edbauer D, Neilson JR, Foster KA, et al. Regulation
of synaptic structure and function by FMRPassociated microRNAs miR-125b and miR-132.
Neuron 2010; 65:373-384.
- 46. Lin Q, Wei W, Coelho CM, et al. The brain-specific
microRNA miR-128b regulates the formation of
fear-extinction memory. Nat Neurosci 2011;
14:1115-1117.
- 47. Gao J, Wang WY, Mao YW, et al. A novel pathway
regulates memory and plasticity via SIRT1 and
miR-134. Nature 2010; 466:1105-1109.
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Mef2-mediated transcription of the miR379–410
cluster regulates activity-dependent
dendritogenesis by fine-tuning Pumilio2 protein
levels. EMBO J 2009; 28:697-710.
- 49. Smrt RD, Szulwach KE, Pfeiffer RL, et al. MicroRNA
miR-137 regulates neuronal maturation by
targeting ubiquitin ligase mind bomb-1. Stem Cells
2010; 28:1060-1070.
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schizophrenia loci. Nat Genet 2011; 43:969-976.
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suppression in the hippocampus evokes
antidepressant-like effects in rats. Prog
Neuropsychopharmacol Biol Psychiatry 2016;
4:96-103.
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MicroRNA-219 modulates NMDA receptormediated neurobehavioral dysfunction. Proc Natl
Acad Sci 2009; 106:3507-3512.
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Opposing actions of environmental enrichment
and Alzheimer's disease on the expression of
hippocampal microRNAs in mouse models. Transl
Psychiatry 2013; 3:1-13.
- 54. Santulli G. microRNA: Medical Evidence From
Molecular Biology to Clinical Practice. In: Qiu L,
Tan EK, Zeng L (eds), microRNAs and
Neurodegenerative Diseases. Springer
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