Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model

Deng, Man-Fei; Zhang, Qingping; Wu, Zhuoze; Ma, Tian; He, Ao-Di; Zhang, Tongmei; Ke, Xiao; Yu, Qiong; Han, Yunyun; Lu, Youming

doi:10.1111/acel.13144

Cited by 29 publications

(23 citation statements)

References 37 publications

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“…miRNAs regulating NMDAR expression have also been reported, for instance, miR-139-5p [ 77 ] and miR-125b [ 78 ] have been involved in synaptic plasticity regulation by binding to mRNA coding for NR2A subunit while miR-539 and miR-34a regulate NR2B subunit of NMDAR [ 79 , 80 ]. Moreover, indirect regulation of NMDAR through miR-128 binding to STIM2 (stromal interaction molecule 2) has also been suggested as a miRNA-mediated mechanism of synaptic plasticity modulation [ 81 ].…”

Section: Mirnas As Mediators Of Synaptic Dysfunction In Admentioning

confidence: 99%

microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

Siedlecki-Wullich

Miñano-Molina

Rodríguez‐Álvarez

2021

Cells

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Pathogenic processes underlying Alzheimer’s disease (AD) affect synaptic function from initial asymptomatic stages, long time before the onset of cognitive decline and neurodegeneration. Therefore, reliable biomarkers enabling early AD diagnosis and prognosis are needed to maximize the time window for therapeutic interventions. MicroRNAs (miRNAs) have recently emerged as promising cost-effective and non-invasive biomarkers for AD, since they can be readily detected in different biofluids, including cerebrospinal fluid (CSF) and blood. Moreover, a growing body of evidence indicates that miRNAs regulate synaptic homeostasis and plasticity processes, suggesting that they may be involved in early synaptic dysfunction during AD. Here, we review the current literature supporting a role of miRNAs during early synaptic deficits in AD, including recent studies evaluating their potential as AD biomarkers. Besides targeting genes related to Aβ and tau metabolism, several miRNAs also regulate synaptic-related proteins and transcription factors implicated in early synaptic deficits during AD. Furthermore, individual miRNAs and molecular signatures have been found to distinguish between prodromal AD and healthy controls. Overall, these studies highlight the relevance of considering synaptic-related miRNAs as potential biomarkers of early AD stages. However, further validation studies in large cohorts, including longitudinal studies, as well as implementation of standardized protocols, are needed to establish miRNA-based biomarkers as reliable diagnostic and prognostic tools.

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Section: Mirnas As Mediators Of Synaptic Dysfunction In Admentioning

confidence: 99%

microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

Siedlecki-Wullich

Miñano-Molina

Rodríguez‐Álvarez

2021

Cells

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“…The type of interneuron that MCs innervate was first proposed to be the basket cell (Sloviter, 1991;Sloviter, 1994) and then other studies used the term "perisomatictargeting" for interneurons that included basket-cells and others, such as axo-axonic cells (Freund and Gulyas, 1997). More recently it has been suggested that MCs activate several interneuron cell types (Hsu et al, 2015) and one is the dendritic-targeting HIPP cell (Deng et al, 2020).…”

Section: B the Gabaergic Neuron Subtype Underlying Optogenetically-ementioning

confidence: 99%

Excitatory effects of dentate gyrus mossy cells on granule cells and area CA3: an vitro and in vivo study in adult mice

Bernstein

Botterill

et al. 2020

Preprint

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Glutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary cell type, granule cells (GCs), and GABAergic neurons which inhibit GCs. Prior studies suggest that the net effect of MCs is mainly to inhibit GCs, leading one to question why direct excitation of GCs is often missed. We hypothesized that MCs do have excitatory effects, but each GC is only excited weakly, at least under most experimental conditions. To address this hypothesis, MC axons were stimulated optogenetically in slices. A brief optogenetic stimulus to MC axons in the inner molecular layer (IML) led to a short-latency field EPSP (fEPSP) in the IML, suggesting there was a direct excitatory effect on GCs. Population spikes were negligible however, consistent with weak excitation. FEPSPs reflected AMPA/NMDA receptor-mediated EPSPs in GCs. EPSPs reached threshold after GC depolarization or facilitating NMDA receptors. GABAA and GABAB receptor-mediated IPSPs often followed EPSPs. At the network level, an conditions. This view is consistent with a network where there is selective activation of GCs, optimal for a function of the DG that has received much attention: pattern separation (Leutgeb et al.

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“…miR-128, a highly enriched miRNA in the CNS, 81 regulates neuronal proliferation and differentiation in the developing neocortex 82 and neuronal excitability in vitro. 83 miR-128 is also involved in multiple neurobiological diseases, such as hypoxic-ischemic brain damage, 84 Alzheimer disease, 85 and spinal cord injury. 86 miR-128 is encoded by two separate genes, miR-128-1 and miR-128-2 genes.…”

Section: Mir-128mentioning

confidence: 99%

MicroRNAs and target genes in epileptogenesis

et al. 2020

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Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms "microRNAs/miRNAs AND epilepsy", "microRNAs/miRNAs AND epileptogenesis", and "microRNAs/miRNAs AND seizure". We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.

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Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model

Cited by 29 publications

References 37 publications

microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

Excitatory effects of dentate gyrus mossy cells on granule cells and area CA3: an vitro and in vivo study in adult mice

MicroRNAs and target genes in epileptogenesis

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