Aronica Eleonora, Gorter Jan A, Jansen Gerard H, van Veelen Cees W M, van Rijen Peter C, Ramkema Marja, Troost Dirk
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Epilepsia. 2003 Jun;44(6):785-95. doi: 10.1046/j.1528-1157.2003.54802.x.
Focal cortical dysplasia (FCD) is known to be a major cause of intractable epilepsy. The cellular mechanism(s) underlying the epileptogenicity of FCD remain largely unknown. Because recent studies indicate that metabotropic glutamate receptor subtypes (mGluRs) play a role in epileptogenesis, we investigated the expression and cellular distribution pattern of mGluRs in FCD specimens.
Immunocytochemical expression of group I and group II mGluR subtypes was investigated in 15 specimens of human FCD obtained during epilepsy surgery.
Strong mGluR1alpha and mGluR5 (group I mGluRs) immunoreactivity (IR) was observed in the majority of FCD specimens in dysplastic as well as in heterotopic neurons. mGluR1alpha was expressed in a subpopulation of neurons (mainly large dysplastic cells), whereas mGluR5 was represented in a higher percentage of dysplastic neuronal cells. Group II mGluRs (mGluR2/3) IR was observed less frequently than that in group I mGluRs and generally appeared in <10% of the dysplastic neurons. IR for all three mGluR subtypes was observed in balloon cells. mGluR2/3 appeared to be most frequently expressed in glial fibrillary acidic protein (GFAP)-positive balloon cells (glial type), and mGluR1alpha, in microtubule-associated protein (MAP)2-positive cells (neuronal type). mGluR5 was present in the majority of balloon cells. Occasionally glial mGluR1alpha IR was observed in bizarre glial cells with di- or multinuclei. Reactive astrocytes were intensively stained, mainly with mGluR5 and mGluR2/3.
The cellular distribution of mGluR subtypes, with high expression of mGluR1alpha and mGluR5 in dysplastic neurons, suggests a possible contribution of group I mGluRs to the intrinsic and high epileptogenicity of dysplastic cortical regions.
局灶性皮质发育不良（FCD）是难治性癫痫的主要病因。FCD致痫性的细胞机制在很大程度上仍不清楚。由于最近的研究表明代谢型谷氨酸受体亚型（mGluRs）在癫痫发生中起作用，我们研究了mGluRs在FCD标本中的表达和细胞分布模式。
在癫痫手术中获取的15例人类FCD标本中，研究了I组和II组mGluR亚型的免疫细胞化学表达。
在大多数FCD标本的发育异常神经元以及异位神经元中观察到强烈的mGluR1α和mGluR5（I组mGluRs）免疫反应性（IR）。mGluR1α在一部分神经元（主要是大型发育异常细胞）中表达，而mGluR5在发育异常神经元细胞中所占比例更高。II组mGluRs（mGluR2/3）IR的观察频率低于I组mGluRs，通常出现在不到10%的发育异常神经元中。在气球样细胞中观察到所有三种mGluR亚型的IR。mGluR2/3似乎最常在胶质纤维酸性蛋白（GFAP）阳性的气球样细胞（胶质细胞类型）中表达，而mGluR1α在微管相关蛋白（MAP）2阳性细胞（神经元类型）中表达。mGluR5存在于大多数气球样细胞中。偶尔在双核或多核的奇异胶质细胞中观察到胶质mGluR1α IR。反应性星形胶质细胞被强烈染色，主要是mGluR5和mGluR2/3。
mGluR亚型的细胞分布，即发育异常神经元中mGluR1α和mGluR5的高表达，提示I组mGluRs可能对发育异常皮质区域的内在和高致痫性有贡献。
