MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer DOI Creative Commons
Igor Delvendahl,

Reetu Daswani,

Jochen Winterer

и другие.

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Май 11, 2025

Abstract MicroRNAs are small, highly conserved non‐coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, synaptic plasticity. MicroRNA 138‐5p (miR‐138‐5p) controls inhibitory transmission in hippocampus is expressed cerebellar excitatory neurons. However, its specific role remains unknown. Here, we investigated cerebellum of mice expressing a sponge construct sequesters endogenous miR‐138‐5p. Mossy fibre stimulation‐evoked EPSCs granule cells were ∼40% larger miR‐138‐5p compared controls. Furthermore, observed miniature EPSC amplitudes, suggesting an increased number functional postsynaptic AMPA receptors. High‐frequency train stimulation revealed enhanced short‐term depression following downregulation. Together with computational modelling, this suggests negative regulation presynaptic release probability. Overall, our results demonstrate suppresses strength through pre‐ mechanisms, providing potentially powerful mechanism for tuning input into cerebellum. image Key points regulators control key cell biological processes including transmission, but their regulating function has remained elusive. study, how microRNA‐138‐5p modulates at adult murine mossy synapses. Downregulation enhances layer increases depression. exerts regulatory both mechanisms by probability boutons, as well receptor numbers cells. These findings provide insights expand understanding microRNA‐dependent

Язык: Английский

Somatic mosaicism and interneuron involvement in mTORopathies DOI

Lilian G Jerow,

Darcy A. Krueger, Christina Groß

и другие.

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0

Dysregulated ac4C modification of mRNA in a mouse model of early-stage Alzheimer’s disease DOI Creative Commons

Haonan Ji,

Hai-Qian Zhou, Jingbo Qie

и другие.

Cell & Bioscience, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 13, 2025

The identification and intervention of Alzheimer's Disease (AD) in its early-stage allows for the timely implementation lifestyle modifications therapeutic strategies. Although dysregulation protein expression has been reported brain from AD patients animal models, underlying mechanisms remain poorly understood. N4-acetylcytidine (ac4C), only known form RNA acetylation eukaryotes, recently shown to regulate mRNA stability translation efficiency. However, ac4C associated with abnormal levels mouse models remains be elucidated. This study investigated modifications, hippocampus 3 6-month-old 5×FAD mice, a model AD, wild-type (WT) littermates. multi-omics analysis was performed: acetylated immunoprecipitation followed by next-generation sequencing (acRIP-seq) identify mRNAs, deep (RNA-seq) quantify abundance, label-free quantitative proteomics assess levels. In addition, we used acRIP-qPCR, regular qPCR western blots verify ac4C, some key genes that were identified high-throughput assays. Proteomic revealed significant change 3-months-old compared WT contrast, RNA-seq indicated there no substantial alterations Strikingly, acRIP-seq notable variations modification on particularly those synaptic structure function, found correlated changes. Genes are essential function cognition, including GRIN1, MAP2, DNAJC6, exhibited reduced without any corresponding changes levels, Moreover, small part dysregulated mRNAs 3-month-old mice mice. Altogether these results may contribute synthesis an AD.

Язык: Английский

Процитировано

0

Regulation of PV interneuron plasticity by neuropeptide-encoding genes DOI Creative Commons
Martijn Selten, C. Bernard,

Diptendu Mukherjee

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

Neuronal activity must be regulated in a narrow permissive band for the proper operation of neural networks. Changes synaptic connectivity and network activity-for example, during learning-might disturb this balance, eliciting compensatory mechanisms to maintain function1-3. In neocortex, excitatory pyramidal cells inhibitory interneurons exhibit robust forms stabilizing plasticity. However, although neuronal plasticity has been thoroughly studied cells4-8, little is known about how adapt persistent changes their activity. Here we describe critical cellular process through which cortical parvalbumin-expressing (PV+) levels. We found that individual PV+ drive bidirectional adjustments number strength synapses received by these cells, specifically from other interneurons. High-throughput profiling ribosome-associated mRNA revealed increasing interneuron leads upregulation two genes encoding multiple secreted neuropeptides: Vgf Scg2. Functional experiments demonstrated VGF critically required activity-dependent scaling onto Our findings reveal an instructive role neuropeptide-encoding regulating connections among adult mouse neocortex.

Язык: Английский

Процитировано

0

Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design DOI

Abdul Wadood Nadeem,

Poonam Sharma, Pramod Gupta

и другие.

Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116964 - 116964

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer DOI Creative Commons
Igor Delvendahl,

Reetu Daswani,

Jochen Winterer

и другие.

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Май 11, 2025

Abstract MicroRNAs are small, highly conserved non‐coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, synaptic plasticity. MicroRNA 138‐5p (miR‐138‐5p) controls inhibitory transmission in hippocampus is expressed cerebellar excitatory neurons. However, its specific role remains unknown. Here, we investigated cerebellum of mice expressing a sponge construct sequesters endogenous miR‐138‐5p. Mossy fibre stimulation‐evoked EPSCs granule cells were ∼40% larger miR‐138‐5p compared controls. Furthermore, observed miniature EPSC amplitudes, suggesting an increased number functional postsynaptic AMPA receptors. High‐frequency train stimulation revealed enhanced short‐term depression following downregulation. Together with computational modelling, this suggests negative regulation presynaptic release probability. Overall, our results demonstrate suppresses strength through pre‐ mechanisms, providing potentially powerful mechanism for tuning input into cerebellum. image Key points regulators control key cell biological processes including transmission, but their regulating function has remained elusive. study, how microRNA‐138‐5p modulates at adult murine mossy synapses. Downregulation enhances layer increases depression. exerts regulatory both mechanisms by probability boutons, as well receptor numbers cells. These findings provide insights expand understanding microRNA‐dependent

Язык: Английский

Процитировано

0