Gyu Hyun Kim, Na-Young Seo, Seung-Ki Kim, Jae-Kyung Won, Yang Hoon Huh, Ji Yeoun Lee, Kea Joo Lee
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引用次数: 0
Abstract
Objective: Focal cortical dysplasia (FCD) is a developmental malformation of the cerebral cortex and a leading cause of drug-resistant epilepsy in children and young adults. Disruption of the excitation-inhibition (E-I) balance is a hallmark of neuronal hyperexcitability in FCD, yet the underlying synaptic ultrastructural changes remain poorly understood. This study aimed to investigate synaptic architecture and associated organelle alterations in epileptogenic cortex affected by FCD.
Methods: Using volume electron microscopy, we performed a detailed morphological assessment of synaptic density, size, and organelle distribution within synapses in the temporal cortical layer III of a patient with FCD. Comparative analyses were conducted between dysplastic and nondysplastic cortical regions.
Results: The dysplastic cortex exhibited a lower density of excitatory synapses but contained unusually large excitatory synapses with an increased number of synaptic vesicles. Inhibitory synapses were positioned farther from the nearest excitatory synapses along distal dendrites, potentially reducing the effectiveness of shunting inhibition in the dysplastic area. Presynaptic boutons in the dysplastic region showed increased mitochondrial density and abnormal mitochondrial morphology, whereas the proportion of postsynaptic protrusions containing a spine apparatus was reduced. These changes suggest potential deficits in intracellular calcium handling, metabolic homeostasis, and synaptic plasticity in the epileptogenic cortex. Additionally, maladaptive myelination was a prominent feature in the dysplastic region.
Significance: This study identifies distinct synaptic and subcellular structural abnormalities in FCD that may contribute to E-I imbalance and neuronal hyperexcitability. These findings provide novel ultrastructural insights into the pathophysiology of FCD and may inform future therapeutic strategies targeting synaptic and metabolic dysfunction.
期刊介绍:
Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.