چکیده:
Astrocyte dysfunction plays a crucial role in epileptogenesis by impacting neuronal excitability and synaptic transmission. The effect of small molecules on cellular functions depends on various factors, including the presence of specific target molecules within different cell types and tissues. This study investigates how specific small molecules impact the survival of astrocytes derived from various brain regions (the neocortex, hippocampus, or amygdala) of patients with medically refractory epilepsy. This study evaluated astrocyte responses to three distinct small molecules (valproate, forskolin, and GSK3 inhibitor/WNT activator CHIR99021), both individually and in combinations, to determine their differential effects on astrocyte survival. Our findings revealed that the effects of small molecules 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 small molecules, 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. Variability in astrocyte responses to small molecules, 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 small molecules in epilepsy.
نوع مطالعه: Original |
موضوع مقاله:
Cellular and molecular Neuroscience
دریافت: 1403/9/24 | پذیرش: 1403/11/3
دریافت: 1403/9/24 | پذیرش: 1403/11/3
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