| Popis |
Studies examining patients with temporal lobe epilepsy (TLE) have discovered heightened levels of neurodegeneration-associated proteins (NAPs), such as those typically correlated with Alzheimer's disease (AD). This finding suggests a potential correlation between the presence of NAPs in the brain and an elevated susceptibility to epileptic seizures. Therefore, the present study aims to gather crucial data to explore and establish the relationship between neurodegeneration and brain tissue excitability. The electrical activity was monitored using the multielectrode array technique (MEA) in the cerebral organoids derived from human induced pluripotent stem cells (hiPSCs). The hiPSCs were obtained from two different individuals, one with familial Alzheimer's disease (AD; nAD = 15) and the second one healthy individual representing the control (WT; nWT = 16). The monitoring of electrical activity involved 15-minute sessions conducted twice a week, from the 9th to the 20th week of differentiation (DW), and was maintained at a constant temperature of 37° C. A significantly higher number of the active electrodes was observed in the AD organoids compared to the healthy controls for both spikes (DW11, P < 0.01; DW12, P < 0.05; DW14, P < 0.05; DW15, P < 0.01) and bursts (DW10, P < 0.05; DW11, P < 0.001; DW12, P < 0.01; DW13, P < 0.01; DW14, P < 0.05). For instance, at DW11, the median percentage of active electrodes exhibiting spikes was 4.24% for the WT and 19.49% for the AD (P < 0.01). Similarly, during the same week of differentiation, the median percentage of active electrodes showing bursts was 1.69% for the WT and 16.95% for the AD organoids (P < 0.001). Moreover, the AD organoids displayed a significant increase in intraburst spike number (DW11, P < 0.05), intraburst interval (DW9, P < 0.05; DW10, P < 0.05; DW14, P < 0.05), and intraburst spike frequency (DW9, P < 0.05; DW10, P < 0.01; DW11, P < 0.001; DW12, P < 0.01). The initial findings indicate that neurodegenerative cerebral organoids display increased neural excitability compared to healthy ones. Further investigation will be carried out to validate these preliminary results and to integrate data on the presence of NAPs in the cerebral organoids, focusing on revealing a connection between neurodegeneration and heightened neuronal excitability of brain tissue.
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