Expression of pannexin 1 and 2 in cortical lesions from intractable epilepsy patients with focal cortical dysplasia.

Abstract

Focal cortical dysplasia (FCD) is a major cause of intractable epilepsy in children however the mechanisms underlying the pathogenesis of FCD and FCD induced epilepsy remain unclear. Increasing evidence suggests that the large-pore ion channels, pannexin 1 (Panx1) and 2 (Panx2), are involved in epilepsy and brain development. In this study, we investigated the expression of Panx1 and Panx2 in surgical samples from patients with FCD type Ia (FCDIa), type IIa (FCDIIa), and type IIb (FCDIIb) and in age-matched autopsy control samples. We found Panx1 mRNA and protein levels were both increased in all these FCD samples. Immunohistochemical analyses revealed that Panx1 was mainly distributed in microcolumn neurons, dysmorphic neurons (DNs), balloon cells (BCs) and reactive astrocytes. Double-labeled staining showed that the Panx1-positive neurons were mostly glutamatergic DNs and occasionally GABAergic normal-appearing neurons. Importantly, the protein levels of Panx1 positively correlated with the frequency of seizures. Intriguingly, the Panx2 mRNA and protein levels were only upregulated in FCDIIb lesions and characteristically expressed on SOX2-positive multipotential BCs. Immunofluorescent experiments identified that Panx2-positive BCs mainly expressed the neuronal differentiation transcription factor MASH1 but not the immature glial marker vimentin. Taken together, our results established a potential role of the specific expression and cellular distribution patterns of Panx1 and Panx2 in FCD-associated epileptogenesis and pathogenesis.

• Authors: Song Li, Zhenle Zang, Jiaojiang He, Xin Chen, Sixun Yu, Yuchun Pei, Zhi Hou, Ning An, Hui Yang, Chunqing Zhang, Shiyong Liu
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 4 Pg. 6883-6895 (Jan 24 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28036289 (Publication Type: Journal Article)

Chemical References

• ASCL1 protein, human
• Basic Helix-Loop-Helix Transcription Factors
• Connexins
• Nerve Tissue Proteins
• PANX1 protein, human
• PANX2 protein, human
• RNA, Messenger
• SOX2 protein, human
• SOXB1 Transcription Factors
• Vimentin

Topics

• Astrocytes (chemistry, pathology)
• Basic Helix-Loop-Helix Transcription Factors (analysis)
• Blotting, Western
• Case-Control Studies
• Cerebral Cortex (chemistry, pathology)
• Child
• Child, Preschool
• Connexins (analysis, genetics)
• Drug Resistant Epilepsy (genetics, metabolism, pathology)
• Epilepsy (genetics, metabolism, pathology)
• Humans
• Immunohistochemistry
• Malformations of Cortical Development, Group I (genetics, metabolism, pathology)
• Nerve Tissue Proteins (analysis, genetics)
• Neurons (chemistry, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• SOXB1 Transcription Factors (analysis)
• Up-Regulation
• Vimentin (analysis)