Neurodegenerácia a elektrická aktivita: analýza metódou multielectrode array

LIŠČÁKOVÁ, Barbora, Andrijana ANGELOVSKI, Olga ŠVECOVÁ, Hana HŘÍBKOVÁ, Jiří SEDMÍK, Dáša BOHAČIAKOVÁ, Petr KLIMEŠ, Martina KOLAJOVÁ, Milan BRÁZDIL and Markéta BÉBAROVÁ. Neurodegenerácia a elektrická aktivita: analýza metódou multielectrode array (Neurodegeneration and electrical activity: analysis using multielectrode array technique). In 99. Fyziologické dny. 2024.

Basic information

• Original name: Neurodegenerácia a elektrická aktivita: analýza metódou multielectrode array
• Name (in English): Neurodegeneration and electrical activity: analysis using multielectrode array technique
• Authors: LIŠČÁKOVÁ, Barbora (703 Slovakia, belonging to the institution), Andrijana ANGELOVSKI (688 Serbia, belonging to the institution), Olga ŠVECOVÁ (203 Czech Republic), Hana HŘÍBKOVÁ (203 Czech Republic, belonging to the institution), Jiří SEDMÍK (203 Czech Republic, belonging to the institution), Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution), Petr KLIMEŠ (203 Czech Republic), Martina KOLAJOVÁ (203 Czech Republic), Milan BRÁZDIL (203 Czech Republic, belonging to the institution) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution).
• Edition: 99. Fyziologické dny, 2024.

Other information

• Original language: Slovak
• Type of outcome: Conference abstract
• Field of Study: 30210 Clinical neurology
• Country of publisher: Slovakia
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Faculty of Medicine
• Keywords (in Czech): neurodegenerácia; elektrická aktivita; cerebrálny organoid
• Keywords in English: neurodegeneration; electrical activity; cerebral organoid

Abstract

Úvod: Epilepsia temporálneho laloku je závažný neurologický stav spojený s neurodegeneráciou a so zmenami v excitabilite. Keďže zvýšené hladiny niektorých proteínov asociovaných s neurodegeneráciou, napríklad kauzálnych proteínov Alzheimerovej choroby (AD), sú spojené so zvýšeným rizikom epileptických záchvatov, predstavuje tkanivo s potenciálom vývoja AD vhodný model pre skúmanie excitačných zmien pri vývoji epilepsie. Metodika: Pre in vitro analýzu elektrickej aktivity a jej zmien v prítomnosti neurodegenerácie boli využité cerebrálne organoidy diferencované z indukovaných pluripotentných buniek pacienta s familiárnou formou AD (nAD = 5) a ze zdravého kontrolního jedince (nWT = 5). Elektrická aktivita bola zaznamenávaná prostredníctvom techniky multielectrode array v diferenciačných dňoch D72 až D139 (37 °C). Následne prebehla analýza záznamu v 5.-15. min, a to detekcia tzv. burstov (skupiny hrotových výbojov nasledujúcich po sebe v krátkom časovom intervale) a štatistická analýza dát (medián, Mann-Whitney test). Výsledky: U AD organoidov bolo u niektorých parametrov zachytené zvýšenie burst aktivity v porovnaní so zdravou kontrolou. Signifikantný rozdiel bol zaznamenaný v počte aktívnych elektród (D100, D105, D107, D114, P < 0,05, napr. D105: WT 1,7 vs. AD 17,0 %), priemernom trvaní burstu (D118: WT 153,3 vs. AD 390,5 ms, P < 0,05), počte burstov (D105: WT 9,5 vs. AD 41,0, P < 0,05) a počte spikov v burste (D114: WT 7,0 vs. AD 13,0, P < 0,05). Záver: Pozorovaný nárast elektrickej aktivity poukazuje na možné zvýšenie excitability v neurálnom tkanive postihnutého neurodegeneráciou.

Abstract (in English)

Introduction: Temporal lobe epilepsy is a serious neurological condition associated with neurodegeneration and changes in excitability. Since increased levels of some proteins associated with neurodegeneration, for example the causal proteins of Alzheimer's disease (AD), are associated with an increased risk of epileptic seizures, tissue with the potential to develop AD represents a suitable model for investigating excitatory changes in the development of epilepsy. Methodology: For in vitro analysis of electrical activity and its changes in the presence of neurodegeneration, cerebral organoids differentiated from induced pluripotent cells of a patient with a familial form of AD (nAD = 5) and from a healthy control individual (nWT = 5) were used. Electrical activity was recorded using the multielectrode array technique on differentiation days D72 to D139 (37°C). Subsequently, the analysis of the record took place in 5.-15. min, namely the detection of so-called bursts (groups of spike discharges following each other in a short time interval) and statistical data analysis (median, Mann-Whitney test). Results: An increase in burst activity was detected in some parameters in AD organoids compared to healthy controls. A significant difference was noted in the number of active electrodes (D100, D105, D107, D114, P < 0.05, e.g. D105: WT 1.7 vs. AD 17.0%), average burst duration (D118: WT 153, 3 vs. AD 390.5 ms, P < 0.05), number of bursts (D105: WT 9.5 vs. AD 41.0, P < 0.05) and number of spikes in a burst (D114: WT 7 .0 vs. AD 13.0, P < 0.05). Conclusion: The observed increase in electrical activity points to a possible increase in excitability in neural tissue affected by neurodegeneration.

Links

• GA24-12028S, research and development project: Name: Atlas Alzheimerovy choroby: Mapování vývoje demence u cerebrálních organoidů pomocí single-cell transkriptomiky

Investor: Czech Science Foundation, Constructing the Developmental Atlas of Alzheimer’s Disease using Cerebral Organoids and Single-Cell Transcriptomics

• LX22NPO5107, research and development project: Name: Národní ústav pro neurologický výzkum

Investor: Ministry of Education, Youth and Sports of the CR, 5.1 EXCELES

• MUNI/A/1343/2022, interní kód MU: Name: Zátěže kardiovaskulárního systému od A po Z

Investor: Masaryk University, Loads on the cardiovascular system from A to Z

• MUNI/A/1547/2023, interní kód MU: Name: Analýza (dys)funkce: od molekul k živému organismu

Investor: Masaryk University, Analysis of (dys)function: from molecules to the living organism

• NU22-04-00366, research and development project: Name: Role neurodegenerace v patogenezi, manifestaci a prognóze MTLE/HS - in vivo, ex vivo a in vitro perspektiva

Investor: Ministry of Health of the CR, The role of neurodegeneration in pathogenesis, manifestations and prognosis of MTLE/HS - in vivo, ex vivo and in vitro perspective, Subprogram 1 - standard