Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex

R. Garbelli, C. Frassoni, D. F. Condorelli, A. Trovato Salinaro, N. Musso, V. Medici, L. Tassi, M. Bentivoglio, R. Spreafico

Research output: Contribution to journalArticle

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Abstract

Background: Gap junctions are specialized channels composed of several connexins, membrane proteins that mediate electrical and metabolic coupling between cells. Previous data have suggested that changes in the expression of Cx43, the main astrocytic Cx isoform, may be involved in seizure activity in human epileptic tissue. However, Cx43 has never been examined in focal cortical dysplasia (FCD) and in other human refractory epilepsies. Methods: We analyzed Cx43 protein localization and Cx43 mRNA levels in surgical specimens of cortex from a cohort of patients with intractable epilepsy vs control nonepileptic tissue. Samples had neuropathologically defined diagnosis of cryptogenic epilepsy or epilepsy secondary to FCD. Results: Cx43 immunoreactivity, which labeled punctate elements, did not reveal distinctive features in cryptogenic epilepsy and FCD type IA and IIA. A peculiar pattern of immunolabeling was instead observed in FCD type IIB, in which large aggregates of Cx43-immunopositive puncta were clustered around subsets of balloon cells and astrocytes. Further characterization revealed that these balloon cells do not express markers of precursor cells, such as CD34. Quantitative real-time reverse transcriptase PCR showed elevated levels of Cx43 transcript in a subgroup (25%) of cryptogenic epilepsy specimens compared to control and FCD ones. Conclusions: Our study points out that a rearrangement of Cx43-positive elements is part of abnormal tissue organization in FCD type IIB, and that cryptogenic epilepsies include forms with increased Cx43 mRNA expression. The data implicate functional consequences of altered Cx43 expression, and therefore of altered gap junctional coupling, in abnormal network properties of subtypes of human refractory epilepsies.

Original languageEnglish
Pages (from-to)895-902
Number of pages8
JournalNeurology
Volume76
Issue number10
DOIs
Publication statusPublished - Mar 8 2011

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Connexin 43
Cerebral Cortex
Malformations of Cortical Development
Epilepsy
Pharmaceutical Preparations
Messenger RNA
Connexins
Gap Junctions
Reverse Transcriptase Polymerase Chain Reaction
Human Activities
Astrocytes
Real-Time Polymerase Chain Reaction
Protein Isoforms
Membrane Proteins
Seizures

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Garbelli, R., Frassoni, C., Condorelli, D. F., Trovato Salinaro, A., Musso, N., Medici, V., ... Spreafico, R. (2011). Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex. Neurology, 76(10), 895-902. https://doi.org/10.1212/WNL.0b013e31820f2da6

Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex. / Garbelli, R.; Frassoni, C.; Condorelli, D. F.; Trovato Salinaro, A.; Musso, N.; Medici, V.; Tassi, L.; Bentivoglio, M.; Spreafico, R.

In: Neurology, Vol. 76, No. 10, 08.03.2011, p. 895-902.

Research output: Contribution to journalArticle

Garbelli, R, Frassoni, C, Condorelli, DF, Trovato Salinaro, A, Musso, N, Medici, V, Tassi, L, Bentivoglio, M & Spreafico, R 2011, 'Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex', Neurology, vol. 76, no. 10, pp. 895-902. https://doi.org/10.1212/WNL.0b013e31820f2da6
Garbelli, R. ; Frassoni, C. ; Condorelli, D. F. ; Trovato Salinaro, A. ; Musso, N. ; Medici, V. ; Tassi, L. ; Bentivoglio, M. ; Spreafico, R. / Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex. In: Neurology. 2011 ; Vol. 76, No. 10. pp. 895-902.
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