Zhang Joyce, Argueta Deneen, Tong Xiaoping, Vinters Harry V, Mathern Gary W, Cepeda Carlos
IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California - Los Angeles, Los Angeles, CA, United States.
Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Neurosci. 2025 Jan 6;18:1486315. doi: 10.3389/fncel.2024.1486315. eCollection 2024.
Once believed to be the culprits of epileptogenic activity, the functional properties of balloon/giant cells (BC/GC), commonly found in some malformations of cortical development including focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC), are beginning to be unraveled. These abnormal cells emerge during early brain development as a result of a hyperactive mTOR pathway and may express both neuronal and glial markers. A paradigm shift occurred when our group demonstrated that BC/GC in pediatric cases of FCDIIb and TSC are unable to generate action potentials and lack synaptic inputs. Hence, their role in epileptogenesis remained obscure. In this review, we provide a detailed characterization of abnormal non-neuronal cells including BC/GC, intermediate cells, and dysmorphic/reactive astrocytes found in FCDIIb and TSC cases, with special emphasis on electrophysiological and morphological assessments. Regardless of pathology, the electrophysiological properties of abnormal cells appear more glial-like, while others appear more neuronal-like. Their morphology also differs in terms of somatic size, shape, and dendritic elaboration. A common feature of these types of non-neuronal cells is their inability to generate action potentials. Thus, despite their distinct properties and etiologies, they share a common functional feature. We hypothesize that, although the exact role of abnormal non-neuronal cells in FCDIIb and TSC remains mysterious, it can be suggested that cells displaying more glial-like properties function in a similar way as astrocytes do, i.e., to buffer K ions and neurotransmitters, while those with more neuronal properties, may represent a metabolic burden due to high energy demands but inability to receive or transmit electric signals. In addition, due to the heterogeneity of these cells, a new classification scheme based on morphological, electrophysiological, and gene/protein expression in FCDIIb and TSC cases seems warranted.
曾经被认为是致痫活动的罪魁祸首，气球样/巨细胞（BC/GC）的功能特性开始被揭示，这种细胞常见于一些皮质发育畸形中，包括IIb型局灶性皮质发育不良（FCDIIb）和结节性硬化症（TSC）。这些异常细胞在脑发育早期由于mTOR通路过度活跃而出现，并且可能同时表达神经元和胶质细胞标志物。当我们的研究小组证明FCDIIb和TSC儿科病例中的BC/GC无法产生动作电位且缺乏突触输入时，发生了范式转变。因此，它们在癫痫发生中的作用仍然不明。在这篇综述中，我们详细描述了在FCDIIb和TSC病例中发现的异常非神经元细胞，包括BC/GC、中间细胞以及发育异常/反应性星形胶质细胞，特别强调了电生理和形态学评估。无论病理情况如何，异常细胞的电生理特性似乎更像胶质细胞，而其他一些则更像神经元细胞。它们的形态在体细胞大小、形状和树突精细度方面也有所不同。这些类型的非神经元细胞的一个共同特征是它们无法产生动作电位。因此，尽管它们具有不同的特性和病因，但它们具有共同的功能特征。我们推测，尽管异常非神经元细胞在FCDIIb和TSC中的确切作用仍然神秘，但可以认为表现出更多胶质细胞样特性的细胞的功能与星形胶质细胞类似，即缓冲钾离子和神经递质，而那些具有更多神经元特性的细胞，由于高能量需求但无法接收或传递电信号，可能代表一种代谢负担。此外，由于这些细胞的异质性，基于FCDIIb和TSC病例中的形态学、电生理学以及基因/蛋白质表达的新分类方案似乎是必要的。
