Developmental effect of RASopathy mutations on neuronal network activity on a chip

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921351" target="_blank" >RIV/00023752:_____/24:43921351 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11120/24:43927264

Result on the web

<a href="https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1388409/full" target="_blank" >https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1388409/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fncel.2024.1388409" target="_blank" >10.3389/fncel.2024.1388409</a>

Result language

angličtina

Original language name

Developmental effect of RASopathy mutations on neuronal network activity on a chip

Original language description

RASopathies are a group of genetic disorders caused by mutations in genes encoding components and regulators of the RAS/MAPK signaling pathway, resulting in overactivation of signaling. RASopathy patients exhibit distinctive facial features, cardiopathies, growth and skeletal abnormalities, and varying degrees of neurocognitive impairments including neurodevelopmental delay, intellectual disabilities, or attention deficits. At present, it is unclear how RASopathy mutations cause neurocognitive impairment and what their neuron-specific cellular and network phenotypes are. Here, we investigated the effect of RASopathy mutations on the establishment and functional maturation of neuronal networks. We isolated cortical neurons from RASopathy mouse models, cultured them on multielectrode arrays and performed longitudinal recordings of spontaneous activity in developing networks as well as recordings of evoked responses in mature neurons. To facilitate the analysis of large and complex data sets resulting from long-term multielectrode recordings, we developed MATLAB-based tools for data processing, analysis, and statistical evaluation. Longitudinal analysis of spontaneous network activity revealed a convergent developmental phenotype in neurons carrying the gain-of-function Noonan syndrome-related mutations Ptpn11D61Y and KrasV14l. The phenotype was more pronounced at the earlier time points and faded out over time, suggesting the emergence of compensatory mechanisms during network maturation. Nevertheless, persistent differences in excitatory/inhibitory balance and network excitability were observed in mature networks. This study improves the understanding of the complex relationship between genetic mutations and clinical manifestations in RASopathies by adding insights into functional network processes as an additional piece of the puzzle.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2024

Confidentiality

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

Name of the periodical

Frontiers in Cellular Neuroscience

ISSN

1662-5102

e-ISSN

1662-5102

Volume of the periodical

18

Issue of the periodical within the volume

"Article number 1388409"

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

1-19

UT code for WoS article

001251158300001

EID of the result in the Scopus database

2-s2.0-85196502371