Změny neuronální elektrické aktivity pod vlivem glutamátu a snížené exprese miR-142-5p

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Title in English Changes of neuronal electrical activity under the effect of glutamate and lower expression of miR-142-5p
Authors

POLEDŇÁKOVÁ Anna GOLIÁŠOVÁ Zita ŠVECOVÁ Olga KRÁL Martin BRÁZDIL Milan BÉBAROVÁ Markéta

Year of publication 2024
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Introduction: Glutamate, the main excitatory neurotransmitter in the CNS, can be used to induce epilepsy in vitro according to some studies. Changes in the expression of some miRNAs, including miR-142-5p, are also involved in the development of epilepsy, making them a possible therapeutic target. The aim of this pilot project was to evaluate the effect of a specific inhibitor (antagomir) against miR-142-5p on neuronal activity, whether spontaneous or increased by glutamate. Methodology: We measured the electrical activity of hippocampal neurons isolated from neonatal rats using the multielectrode array (MEA) technique from day 7 in vitro (DIV) at a sampling frequency of 25 kHz. On DIV 13, 10 µM glutamate was applied to the selected group of MEA chips (10-min application followed by washing), and 6 days before the planned end of imaging, we applied 30 nM antagomir to reduce the expression of miR-142-5p (followed by measurements 1, 2 and 5th day after its application). Analyzed parameters include the frequency of spike potentials (spikes) and the number of active electrodes. Results: During cultivation, there was a significant increase in the frequency of spikes and the number of active electrodes both in control MEA chips and in chips with transient application of glutamate (n=7, P?0.05, respectively n=8, P?0.01) , but no difference was apparent between control and glutamate. Spike frequency after application of 30 nM antagomir showed a non-significant downward trend, whereas no similar decrease was evident in controls; the number of active electrodes was stable. Conclusion: According to our data so far, the transient application of glutamate cannot be used as a model of epilepsy in vitro. Pilot data point to a possible inhibitory effect of an antagomir against miR-142-5p on the spontaneous electrical activity of neurons. If this is confirmed by the final data, it will be possible to consider reducing the expression of this miRNA as an alternative treatment for drug-resistant epilepsy.
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