microRNA-34c is a novel target to treat dementias

Zovoilis, Athanasios; Agbemenyah, Hope Yao; Agís‐Balboa, Roberto Carlos; Stilling, Roman M.; Edbauer, Dieter; Rao, Pooja; Farinelli, Laurent; Delalle, Ivana; Schmitt, Andrea; Falkai, Peter; Bahari‐Javan, Sanaz; Burkhardt, Susanne; Sananbenesi, Farahnaz; Fischer, André

doi:10.1038/emboj.2011.327

Cited by 306 publications

(290 citation statements)

References 47 publications

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“…The abundant neuronal miR-34c was shown to increase with ageing and contribute to impairments in fear-conditioning memory that are usually observed with increased age. Importantly, this phenotype could be rescued by injection of miR34c inhibitors into the hippocampus [16]. In this study, the miR-34c effect was attributed at least partially to decreased levels of the miR-34c target SIRT1 in the hippocampal formation [16].…”

Section: (I) Mir-132mentioning

confidence: 75%

“…Interestingly, Sirt1 is also involved in the repression of other miRNA transcripts, e.g. pri-miR-138-1, and is itself a target of miR-138 [15] and miR-34 [16]. This suggests the existence of sophisticated feedback systems involving miRNAs and transcription factors as already described for developing neurons [17].…”

Section: Regulation Of Mirnas By Neuronal Activity (A) Activity-depenmentioning

confidence: 98%

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MicroRNAs and synaptic plasticity—a mutual relationship

Aksoy‐Aksel

Zampa

Schratt

2014

Phil. Trans. R. Soc. B

108

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MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain-and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

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Section: (I) Mir-132mentioning

confidence: 75%

Section: Regulation Of Mirnas By Neuronal Activity (A) Activity-depenmentioning

confidence: 98%

MicroRNAs and synaptic plasticity—a mutual relationship

Aksoy‐Aksel

Zampa

Schratt

2014

Phil. Trans. R. Soc. B

108

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“…Among these 269 miRNAs, 55 were differentially expressed in the hippocampus between the 2‐ and 18‐month‐old mice. Among miRNAs regulated by age, miR‐34 is known to be upregulated in aged hippocampus and targets Sirt1 to regulate memory function (Zovoilis et al ., 2011). In this study, we provided a second possible example of miRNA‐associated memory regulation through miR‐204.…”

Section: Discussionmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

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SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

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“…The alteration of miR132-3p in Alzheimer's disease brain was suggested to be associated to neuronal cells containing hyperphosphorylated tau, and that a potential mRNA target of miR132-3p was the transcription factor FOXO1 [29]. Another miRNA, miR-34c was found to be increased in the hippocampus of both AD patients and AD mouse models, and identified as key regulator of learning-induced gene expression [30]. Next miR-34c was revealed to target a gene associated to risk factor in sporadic AD [31] named TREM2, which is reduced in human AD brains [32].…”

mentioning

confidence: 99%

Alzheim(i)R: MicroRNAs in Alzheimer’s Disease

Barbato¹

2014

J Cytol Histol

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microRNA-34c is a novel target to treat dementias

Cited by 306 publications

References 47 publications

MicroRNAs and synaptic plasticity—a mutual relationship

MicroRNAs and synaptic plasticity—a mutual relationship

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

Alzheim(i)R: MicroRNAs in Alzheimer’s Disease

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