Basic and clinical neuroscience · 2025
The Impact of Small Molecule on the Astrocyte's Viability Derived From Epileptic Brain Tissues.
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Momeni Javad, Hosseini Elham, Khaleghi Ghadiri Maryam, Samini Fariborz, Tabibkhooei Alireza, Gorji Ali, Sahab Negah Sajad
Аннотация
INTRODUCTION: Astrocyte dysfunction plays a crucial role in epileptogenesis by impacting neuronal excitability and synaptic transmission. This study investigates how specific small molecules (SMs) affect the survival of astrocytes derived from various brain regions (the neocortex, hippocampus, or amygdala) of patients with medically refractory epilepsy.
METHODS: This study evaluated astrocyte responses to three distinct SMs (valproate, forskolin, and GSK3 inhibitor/WNT activator CHIR99021), individually or in combined forms, to determine their differential effects on astrocyte survival.
RESULTS: The effects of SMs on astrocyte survival varied based on the brain tissue source and individual patient differences. Astrocytes from the amygdala of two patients showed heightened sensitivity to the SMs, while astrocytes from the neocortex of one patient exhibited decreased viability following treatment with CHIR99021 and valproate. Moreover, astrocytes from the hippocampus exhibited a significant decrease in viability in one patient, whereas no significant changes were observed in other patients.
CONCLUSION: Variability in astrocyte responses to SMs, influenced by brain region and patient differences, may highlight their role in shaping diverse therapeutic outcomes in individuals. Further studies are required to clarify the factors involved in the different behaviors of astrocytes in response to SMs in epilepsy.
METHODS: This study evaluated astrocyte responses to three distinct SMs (valproate, forskolin, and GSK3 inhibitor/WNT activator CHIR99021), individually or in combined forms, to determine their differential effects on astrocyte survival.
RESULTS: The effects of SMs on astrocyte survival varied based on the brain tissue source and individual patient differences. Astrocytes from the amygdala of two patients showed heightened sensitivity to the SMs, while astrocytes from the neocortex of one patient exhibited decreased viability following treatment with CHIR99021 and valproate. Moreover, astrocytes from the hippocampus exhibited a significant decrease in viability in one patient, whereas no significant changes were observed in other patients.
CONCLUSION: Variability in astrocyte responses to SMs, influenced by brain region and patient differences, may highlight their role in shaping diverse therapeutic outcomes in individuals. Further studies are required to clarify the factors involved in the different behaviors of astrocytes in response to SMs in epilepsy.