PMID- 31625272 OWN - NLM STAT- MEDLINE DCOM- 20210113 LR - 20231113 IS - 1474-9726 (Electronic) IS - 1474-9718 (Print) IS - 1474-9718 (Linking) VI - 19 IP - 1 DP - 2020 Jan TI - MicroRNA-134-5p inhibition rescues long-term plasticity and synaptic tagging/capture in an Abeta(1-42)-induced model of Alzheimer's disease. PG - e13046 LID - 10.1111/acel.13046 [doi] LID - e13046 AB - Progressive memory loss is one of the most common characteristics of Alzheimer's disease (AD), which has been shown to be caused by several factors including accumulation of amyloid beta peptide (Abeta) plaques and neurofibrillary tangles. Synaptic plasticity and associative plasticity, the cellular basis of memory, are impaired in AD. Recent studies suggest a functional relevance of microRNAs (miRNAs) in regulating plasticity changes in AD, as their differential expressions were reported in many AD brain regions. However, the specific role of these miRNAs in AD has not been elucidated. We have reported earlier that late long-term potentiation (late LTP) and its associative mechanisms such as synaptic tagging and capture (STC) were impaired in Abeta (1-42)-induced AD condition. This study demonstrates that expression of miR-134-5p, a brain-specific miRNA is upregulated in Abeta (1-42)-treated AD hippocampus. Interestingly, the loss of function of miR-134-5p restored late LTP and STC in AD. In AD brains, inhibition of miR-134-5p elevated the expression of plasticity-related proteins (PRPs), cAMP-response-element binding protein (CREB-1) and brain-derived neurotrophic factor (BDNF), which are otherwise downregulated in AD condition. The results provide the first evidence that the miR-134-mediated post-transcriptional regulation of CREB-1 and BDNF is an important molecular mechanism underlying the plasticity deficit in AD; thus demonstrating the critical role of miR-134-5p as a potential therapeutic target for restoring plasticity in AD condition. CI - (c) 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. FAU - Baby, Nimmi AU - Baby N AD - Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. AD - Centre for Life Sciences, Life Sciences Institute, Neurobiology Programme, National University of Singapore, Singapore. FAU - Alagappan, Nithyakalyani AU - Alagappan N AD - Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. AD - Centre for Life Sciences, Life Sciences Institute, Neurobiology Programme, National University of Singapore, Singapore. FAU - Dheen, Shaikali Thameem AU - Dheen ST AD - Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. FAU - Sajikumar, Sreedharan AU - Sajikumar S AUID- ORCID: 0000-0002-5761-8982 AD - Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. AD - Centre for Life Sciences, Life Sciences Institute, Neurobiology Programme, National University of Singapore, Singapore. LA - eng GR - 0037/National Medical Research Council (NMRC)/International GR - 2017/National Medical Research Council (NMRC)/International GR - 3/Ministry of Education-Tier.3 (MoE-Tier.3)/International GR - MOE2017-T3-1-002/Ministry of Education-Tier.3 (MoE-Tier.3)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191017 PL - England TA - Aging Cell JT - Aging cell JID - 101130839 RN - 0 (MicroRNAs) RN - 0 (Mirn134 microRNA, mouse) SB - IM MH - Alzheimer Disease/*genetics MH - Animals MH - Disease Models, Animal MH - Male MH - Mice MH - MicroRNAs/*genetics MH - Rats MH - Rats, Wistar PMC - PMC6974725 OTO - NOTNLM OT - Alzheimer's disease OT - Abeta(1-42) OT - brain-derived neurotrophic factor OT - cAMP response element-binding protein OT - long-term potentiation OT - miRNA OT - synaptic tagging COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2019/10/19 06:00 MHDA- 2021/01/14 06:00 PMCR- 2020/01/01 CRDT- 2019/10/19 06:00 PHST- 2019/01/25 00:00 [received] PHST- 2019/07/31 00:00 [revised] PHST- 2019/08/28 00:00 [accepted] PHST- 2019/10/19 06:00 [pubmed] PHST- 2021/01/14 06:00 [medline] PHST- 2019/10/19 06:00 [entrez] PHST- 2020/01/01 00:00 [pmc-release] AID - ACEL13046 [pii] AID - 10.1111/acel.13046 [doi] PST - ppublish SO - Aging Cell. 2020 Jan;19(1):e13046. doi: 10.1111/acel.13046. Epub 2019 Oct 17.