MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice

Boscher, Emmanuelle; Goupil, Claudia; Pétry, Séréna; Keraudren, Rémi; Loiselle, Andréanne; Planel, Emmanuel; Hébert, Sébastien S.

doi:10.3389/fnins.2020.591138

Cited by 16 publications

(12 citation statements)

References 57 publications

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“…Our model of miR138-5p being a positive regulator of memory is consistent with results obtained from previous studies performed in mice ( Boscher et al, 2020 ; Tatro et al, 2013 ; Tian et al, 2018 ). Moreover, GWAS analysis identified miR138-5p as a putative regulator of human memory performance ( Schröder et al, 2014 ).…”

Section: Discussionsupporting

confidence: 92%

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

Daswani

Gilardi

Soutschek

et al. 2022

eLife

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The proper development and function of neuronal circuits relies on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, e.g. schizophrenia. microRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated miR138-5p inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR138-5p target gene. Our findings suggest that miR138-5p is a critical regulator of PV interneuron function in mice, with implications for cognition and schizophrenia. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.

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Section: Discussionsupporting

confidence: 92%

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

Daswani

Gilardi

Soutschek

et al. 2022

eLife

View full text Add to dashboard Cite

show abstract

“…Our model of miR-138-5p being a positive regulator of memory is consistent with results obtained from previous studies performed in mice (Boscher et al, 2020; Tatro et al, 2013; Tian et al, 2018). Moreover, GWAS analysis identified miR-138-5p as a putative regulator of human memory performance (Schroder et al, 2014).…”

Section: Discussionsupporting

confidence: 92%

microRNA-138 controls hippocampal interneuron function and short-term memory

Daswani¹,

Gilardi²,

Soutschek³

et al. 2021

Preprint

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A tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission is critical for neural circuit assembly and function. microRNAs control excitatory neuron function, but their role in inhibitory interneurons is unknown. Here, we show that miR-138-5p regulates the expression of presynaptic genes in hippocampal parvalbumin-expressing inhibitory interneurons to control short-term memory. Our finding suggests a critical role for miR-138-5p in disorders of impaired E/I balance, such as autism and schizophrenia.

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“…Overall, human and mouse data analyses revealed ten potential miRNAs designated as synaptosomal miRNAs shown in Supplementary Fig. 6 are actively involved in several neural functions [53][54][55][56][57][58] .…”

Section: Discussionmentioning

confidence: 99%

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

et al. 2022

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MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes and cytosolic fractions from postmortem brains of AD and unaffected control (UC) samples and analyzed them using a global Affymetrix miRNAs microarray platform. A group of miRNAs significantly differed (P < 0.0001) with high fold changes variance (+/− >200-fold) in their expressions in different comparisons: (1) UC synaptosome vs UC cytosol, (2) AD synaptosomes vs AD cytosol, (3) AD cytosol vs UC cytosol, and (4) AD synaptosomes vs UC synaptosomes. MiRNAs data analysis revealed that some potential miRNAs were consistently different across sample groups. These differentially expressed miRNAs were further validated using AD postmortem brains, brains of APP transgenic (Tg2576), Tau transgenic (P301L), and wild-type mice. The miR-501-3p, miR-502-3p, and miR-877-5p were identified as potential synaptosomal miRNAs upregulated with disease progression based on AD Braak stages. Gene Ontology Enrichment and Ingenuity Pathway Analysis of synaptosomal miRNAs showed the involvement of miRNAs in nervous system development, cell junction organization, synapse assembly formation, and function of GABAergic synapse. This is the first description of synaptic versus cytosolic miRNAs in AD and their significance in synapse function.

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MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice

Cited by 16 publications

References 57 publications

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

microRNA-138 controls hippocampal interneuron function and short-term memory

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

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