MicroRNA-218 instructs proper assembly of hippocampal networks DOI Creative Commons
Seth R. Taylor, Mariko Kobayashi, Antonietta Vilella

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 25, 2022

ABSTRACT The assembly of the mammalian brain is orchestrated by temporally coordinated waves gene expression. A key aspect this developmental program mediated at post-transcriptional level microRNAs (miRNAs). Deletion neuronal enriched miRNAs induces strong phenotypes, and multiple reports have found altered levels in patients with neurodevelopmental disorders. However, cellular molecular mechanisms used to instruct proper development remain largely unexplored. Here, through screens, we identified miR-218 as a critical regulator hippocampal mice. MiR-218 highly expressed hippocampus both excitatory principal neurons GABAergic inhibitory interneurons. Transient inhibition early life results an adult heightened network activity predisposition seizures. We RNA-seq FACS-seq (fluorescence-activated cell sorting followed RNA-seq) identify global type-specific changes expression absence narrow down which processes would lead long-term instability. find that disruption depolarizing signaling, structural defects dendritic spines, intrinsic membrane excitability. Finally, conditional knockout interneurons, but not pyramidal sufficient recapitulate effects on stability. Taken together, data suggest orchestrates produce stable adult, primarily regulating interneuron function postnatal life.

Language: Английский

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases DOI Open Access
Giulia Gentile, Giovanna Morello, Valentina La Cognata

et al.

Journal of Personalized Medicine, Journal Year: 2022, Volume and Issue: 12(5), P. 770 - 770

Published: May 10, 2022

Alzheimer’s disease (AD), Parkinson’s (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well the lack effective biomarkers therapeutic treatments. In last decade, microRNAs (miRNAs) have gained considerable interest in diagnostics therapy NDs, owing to their aberrant expression ability target multiple molecules pathways. Here, we provide an overview dysregulated miRNAs fluids (blood or cerebrospinal fluid) nervous tissue AD, PD, ALS patients. By emphasizing those that commonly these highlight potential role therapeutical targets describe use antisense oligonucleotides miRNA therapies.

Language: Английский

Citations

48
Non-coding RNA in the wiring and remodeling of neural circuits DOI Creative Commons
Michael Soutschek, Gerhard Schratt

Neuron, Journal Year: 2023, Volume and Issue: 111(14), P. 2140 - 2154

Published: May 24, 2023

Language: Английский

Citations

38
MicroRNA-218-5p-Ddx41 axis restrains microglia-mediated neuroinflammation through downregulating type I interferon response in a mouse model of Parkinson’s disease DOI Creative Commons
Danlei Wang,

Hongling Gao,

Qixiong Qin

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 16, 2024

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in substantia nigra (SN). Microglia-mediated neuroinflammation has been largely considered one main factors to PD pathology. MicroRNA-218-5p (miR-218-5p) microRNA that plays role neurodevelopment and function, while its potential function remains unclear. Methods We explore involvement miR-218-5p 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. The agomir used for overexpression was delivered into (SN) bilateral stereotaxic infusions. microglial inflammation SN determined using Western blotting immunofluorescence. Motor assessed rotarod test. RNA sequencing (RNA-seq) performed pathways regulated miR-218-5p. target genes were predicted TargetScan confirmed dual luciferase reporter assays. effects on related verified murine microglia-like BV2 cells. To stimulate cells, SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP + ) conditioned media (CM) collected. Results MiR-218-5p expression reduced both MPTP-induced mice MPP -treated significantly alleviated inflammation, DA neurons, motor dysfunction. sequence gene set enrichment analysis showed type I interferon (IFN-I) upregulated mice, this upregulation reversed overexpression. A assay Ddx41 In vitro, or knockdown inhibited IFN-I response inflammatory cytokines stimulated -CM. Conclusions suppresses microglia-mediated preserves via /IFN-I. Hence, miR-218-5p- promising therapeutic PD.

Language: Английский

Citations

11
Advances in biosensors for major depressive disorder diagnostic biomarkers DOI
Tao Dong,

Chenghui Yu,

Qi Mao

et al.

Biosensors and Bioelectronics, Journal Year: 2024, Volume and Issue: 258, P. 116291 - 116291

Published: April 16, 2024

Language: Английский

Citations

9
MicroRNA-218 instructs proper assembly of hippocampal networks DOI Creative Commons
Seth R. Taylor, Mariko Kobayashi, Antonietta Vilella

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Oct. 20, 2023

The assembly of the mammalian brain is orchestrated by temporally coordinated waves gene expression. Post-transcriptional regulation microRNAs (miRNAs) a key aspect this program. Indeed, deletion neuron-enriched miRNAs induces strong developmental phenotypes, and miRNA levels are altered in patients with neurodevelopmental disorders. However, mechanisms used to instruct development remain largely unexplored. Here, we identified miR-218 as critical regulator hippocampal assembly. MiR-218 highly expressed hippocampus enriched both excitatory principal neurons (PNs) GABAergic inhibitory interneurons (INs). Early life inhibition results an adult predisposition seizures. Changes expression absence suggest that network impaired. find disruption early depolarizing signaling, structural defects dendritic spines, intrinsic membrane excitability. Conditional knockout Mir218-2 INs, but not PNs, sufficient recapitulate long-term instability. Finally, de-repressing Kif21b Syt13, two targets, phenocopies effects on synchronous activity induced inhibition. Taken together, data orchestrates formative events PNs INs produce stable networks.

Language: Английский

Citations

12
Remote ischemic conditioning alleviates chronic cerebral hypoperfusion-induced cognitive decline and synaptic dysfunction via the miR-218a-5p/SHANK2 pathway DOI
Ning Li, Chang­hong Ren, Sijie Li

et al.

Progress in Neurobiology, Journal Year: 2023, Volume and Issue: 230, P. 102514 - 102514

Published: Aug. 11, 2023

Language: Английский

Citations

10
Identification of ARHGEF11 (PDZ-RhoGEF) as an in vivo regulator of synapses and cognition DOI Creative Commons
Kathryn J. Bjornson, Bailey A. Kermath, Michael E. Cahill

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 21, 2025

Given the influence of cognitive abilities on life outcomes, there is inherent value in identifying genes involved controlling learning and memory. Further, dysfunction a core feature many neuropsychiatric disorders. Here, we use combinatory silico approach to identify human gene targets that will have an especially high likelihood individually directly impacting cognition. This broad unbiased screen led specific identification ARHGEF11 , which encodes PDZ-RhoGEF. PDZ-RhoGEF largely RhoA-specific activator highly enriched dendritic spines, recent work identified hyperexpression prefrontal cortex bipolar disorder subjects, disease characterized by early emergence persistence scope dysfunction. characterize effects synaptic behavioral phenotypes, molecular biochemical mechanisms control PDZ-RhoGEF’s expression, spatial localization, enzymatic activity. Importantly, our direct regulators (miR-132 DISC1) themselves been repeatedly implicated phenotypes humans, including those caused several Taken together, findings indicate key convergence point among multiple cognition-relevant signaling cascades with potential translational significance.

Language: Английский

Citations

0
The potential role of miRNAs in the pathogenesis of schizophrenia – A focus on signaling pathways interplay DOI
Mohamed Bakr Zaki, Ahmed I. Abulsoud, Alaa Ashraf

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 254, P. 155102 - 155102

Published: Jan. 9, 2024

Language: Английский

Citations

3
Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis DOI

Dipan Maity,

Ravinder K. Kaundal

Neurological Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Language: Английский

Citations

3
microRNA-dependent regulation of gene expression in GABAergic interneurons DOI Creative Commons
Karolina Kołosowska, Gerhard Schratt, Jochen Winterer

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 5, 2023

Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal local inhibitory interneurons those circuits. Gamma-aminobutyric acid (GABA)ergic are remarkably heterogeneous population, comprising subclasses based morphological, electrophysiological, molecular features, with differential connectivity activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for plasticity. miRNAs large group small non-coding RNAs (21-24 nucleotides) acting as negative regulators mRNA translation stability. However, while miRNA-dependent regulation in neurons has been described heretofore several studies, understanding the role is only beginning to emerge. Recent research demonstrated that differentially expressed interneuron subclasses, vitally migration, maturation, survival during embryonic crucial cognitive function memory formation. In this review, we discuss recent progress function. We aim shed light onto mechanisms by which GABAergic contribute sculpting circuits, how dysregulation may underlie emergence numerous neurodevelopmental neuropsychiatric disorders.

Language: Английский

Citations

8