Effect of specific antagomirs targeting miRNA-142-5p and miRNA-142-3p on neuroelectrophysiological parameters

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00142647" target="_blank" >RIV/00216224:14110/25:00142647 - isvavai.cz</a>

Result on the web

<a href="https://www.ecnp.eu/congress2025/programme/provisional-programme/#!abstractdetails/0000695360" target="_blank" >https://www.ecnp.eu/congress2025/programme/provisional-programme/#!abstractdetails/0000695360</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Effect of specific antagomirs targeting miRNA-142-5p and miRNA-142-3p on neuroelectrophysiological parameters

Original language description

Introduction: Epileptic seizures arise from an imbalance favouring excitatory neurotransmission and manifest electrophysiologically as excessive hypersynchronous neuronal activity, including spike potentials and their clustering into bursts. Targeting specific microRNAs (miRNAs) regulating neuronal proteins post-transcriptionally is a novel therapeutic approach in neurophysiology and epileptology. Currently, about 20 miRNAs are under investigation for their potential to reduce epileptiform activity. In this pilot study, we evaluated the effects of inhibitors (antagomirs) targeting miRNA-142-5p and miRNA-142-3p on spontaneous neuronal electrical activity. Methods: Spontaneous activity of hippocampal neurons isolated from neonatal rats was recorded using the multi-electrode array technique from day 7 in vitro (the measuring day 0, D0), the sampling frequency of 25 kHz; 5 min stabilisation + 10 min recording for the analysis. On day 21 in vitro (D14), we applied 300 nmol antagomir targeting either miRNA-142-5p or miRNA-142-3p. Recording was ongoing after the application on D16 and D17. The following parameters were evaluated: spike frequency, burst count, duration and frequency, intraburst spike number and frequency, and the number of active electrodes detecting spikes or bursts. Data were normalized to D14. Since normal data distribution was rejected (the Shapiro-Wilk test), median ± interquartile range was used to characterize the data and the Mann-Whitney test was used to test statistical significance. Results: Between D0 and D14 we observed a significant increase in spike frequency in both miRNA-142-5p data groups (controls: P &lt; 0.01, n = 12; antagomir-treated: P &lt; 0.001, n = 10) and miRNA-3p groups (controls: P &lt; 0.05, n = 11; antagomir-treated: P &lt; 0.001, n = 11). In the samples treated with the antagomir targeting miRNA-142-5p, a 31% reduction in spike frequency was observed compared to controls two days after treatment (D16; P &lt; 0.05); burst analysis did not reveal any significant changes between antagomir-treated and control samples. In samples treated with antagomir targeting miRNA-142-3p, spike frequency was reduced by 34% and 27% compared to controls on D16 and D17, respectively (P &lt; 0.05). On D16, the antagomir-treated group also exhibited a significant reduction in the number of active electrodes with burst activity, burst count and frequency, as well as in intraburst spike count and intraburst spike frequency (P &lt; 0.05, n = 8) in comparison with controls (n = 8). Conclusion: While the miRNA-142-5p antagomir showed only a minor inhibitory effect on spontaneous neuronal activity, the miRNA-142-3p antagomir significantly reduced multiple electrophysiological parameters, suggesting its potential as a candidate for further therapeutic exploration in epilepsy research. To our best knowledge, these findings represent the first direct link between the miRNA-142-3p expression and suppression of neuronal electrical activity.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů