PMID- 22926857
OWN - NLM
STAT- MEDLINE
DCOM- 20121101
LR  - 20220321
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 72
IP  - 2
DP  - 2012 Aug
TI  - miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model.
PG  - 269-77
LID - 10.1002/ana.23588 [doi]
AB  - OBJECTIVE: Alzheimer disease (AD) brains are deficient in brain-derived 
      neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. 
      MicroRNAs (miRNAs) are  approximately 22-nucleotide small noncoding RNAs that control a variety 
      of physiological and disease processes. Here, we show that miR-206 regulates BDNF 
      and memory function in AD mice. METHODS: Expression of miRNAs was analyzed in 
      Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a 
      selected miRNA was validated by in silico prediction, target gene luciferase 
      assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor 
      of miR-206 (antagomir), was injected into the third ventricle of Tg2576 mice, 
      after which memory function, synaptogenesis, neurogenesis, and target gene 
      expression were assessed. For noninvasive delivery, antagomirs were administered 
      intranasally. RESULTS: The brains of Tg2576 mice and the temporal cortex of human 
      AD brains had increased levels of miR-206. This miRNA targeted BDNF transcripts, 
      and AM206 prevented the detrimental effects of amyloid-beta42 on BDNF and dendritic 
      spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral 
      ventricles of AD mice increased the brain levels of BDNF and improved their 
      memory function. In parallel, AM206 enhanced the hippocampal synaptic density and 
      neurogenesis. Furthermore, intranasally administered AM206 also reached the brain 
      and increased BDNF levels and memory function in AD mice. INTERPRETATION: Our 
      findings demonstrate a novel miRNA-dependent regulation of BDNF in AD and suggest 
      possible therapeutic approaches, such as noninvasive intranasal delivery of 
      AM206.
CI  - Copyright (c) 2012 American Neurological Association.
FAU - Lee, Soon-Tae
AU  - Lee ST
AD  - Department of Neurology, Biomedical Research Institute, Seoul National University 
      Hospital, Seoul, South Korea.
FAU - Chu, Kon
AU  - Chu K
FAU - Jung, Keun-Hwa
AU  - Jung KH
FAU - Kim, Jin Hee
AU  - Kim JH
FAU - Huh, Ji-Young
AU  - Huh JY
FAU - Yoon, Hyejin
AU  - Yoon H
FAU - Park, Dong-Kyu
AU  - Park DK
FAU - Lim, Ji-Yeon
AU  - Lim JY
FAU - Kim, Jeong-Min
AU  - Kim JM
FAU - Jeon, Daejong
AU  - Jeon D
FAU - Ryu, Hoon
AU  - Ryu H
FAU - Lee, Sang Kun
AU  - Lee SK
FAU - Kim, Manho
AU  - Kim M
FAU - Roh, Jae-Kyu
AU  - Roh JK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 
      ((5-(2-((benzoyloxycarbonylethylamino)methyl)-4-trifluoromethylphenyl)pyridin-3-yl)acetic 
      acid)
RN  - 0 (Benzylamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (MIRN206 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (Synaptophysin)
RN  - 2679MF687A (Niacin)
SB  - IM
MH  - Alzheimer Disease/drug therapy/genetics/*metabolism/*pathology
MH  - Animals
MH  - Benzylamines/therapeutic use
MH  - Brain/drug effects/*metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dendritic Spines/drug effects/pathology
MH  - Disease Models, Animal
MH  - Fear/drug effects/psychology
MH  - Gene Expression Regulation/genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Learning/drug effects
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Transgenic
MH  - MicroRNAs/*metabolism
MH  - Microarray Analysis
MH  - Neurogenesis/drug effects
MH  - Niacin/analogs & derivatives/therapeutic use
MH  - Oligodeoxyribonucleotides, Antisense/therapeutic use
MH  - Statistics, Nonparametric
MH  - Synaptophysin/metabolism
EDAT- 2012/08/29 06:00
MHDA- 2012/11/02 06:00
CRDT- 2012/08/29 06:00
PHST- 2012/08/29 06:00 [entrez]
PHST- 2012/08/29 06:00 [pubmed]
PHST- 2012/11/02 06:00 [medline]
AID - 10.1002/ana.23588 [doi]
PST - ppublish
SO  - Ann Neurol. 2012 Aug;72(2):269-77. doi: 10.1002/ana.23588.