Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans

Frederic Collignon, Nicholas M. Wetjen, Aaron Cohen-Gadol, Gregory D. Cascino, Joseph Parisi, Fredric B. Meyer, W. Richard Marsh, Patrick Roche, Stephen D. Weigand

Research output: Contribution to journalArticle

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Abstract

Object. The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods. The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures - that is, staining intensity, percentage of positively stained cells, and immunoreactive score - Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p <0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p <0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions. The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.

Original languageEnglish (US)
Pages (from-to)77-87
Number of pages11
JournalJournal of Neurosurgery
Volume105
Issue number1
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Connexins
Temporal Lobe Epilepsy
Hippocampus
Seizures
Connexin 43
Gap Junctions
Staining and Labeling
Dentate Gyrus
Sclerosis
Astrocytes
Dissection
Epilepsy
Maintenance
Neurons

Keywords

  • Amygdalohippocampectomy
  • Gap junction
  • Hippocampus
  • Seizure

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Collignon, F., Wetjen, N. M., Cohen-Gadol, A., Cascino, G. D., Parisi, J., Meyer, F. B., ... Weigand, S. D. (2006). Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans. Journal of Neurosurgery, 105(1), 77-87. https://doi.org/10.3171/jns.2006.105.1.77

Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans. / Collignon, Frederic; Wetjen, Nicholas M.; Cohen-Gadol, Aaron; Cascino, Gregory D.; Parisi, Joseph; Meyer, Fredric B.; Marsh, W. Richard; Roche, Patrick; Weigand, Stephen D.

In: Journal of Neurosurgery, Vol. 105, No. 1, 2006, p. 77-87.

Research output: Contribution to journalArticle

Collignon, F, Wetjen, NM, Cohen-Gadol, A, Cascino, GD, Parisi, J, Meyer, FB, Marsh, WR, Roche, P & Weigand, SD 2006, 'Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans', Journal of Neurosurgery, vol. 105, no. 1, pp. 77-87. https://doi.org/10.3171/jns.2006.105.1.77
Collignon, Frederic ; Wetjen, Nicholas M. ; Cohen-Gadol, Aaron ; Cascino, Gregory D. ; Parisi, Joseph ; Meyer, Fredric B. ; Marsh, W. Richard ; Roche, Patrick ; Weigand, Stephen D. / Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans. In: Journal of Neurosurgery. 2006 ; Vol. 105, No. 1. pp. 77-87.
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abstract = "Object. The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods. The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures - that is, staining intensity, percentage of positively stained cells, and immunoreactive score - Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p <0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p <0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions. The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.",
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AU - Wetjen, Nicholas M.

AU - Cohen-Gadol, Aaron

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AU - Parisi, Joseph

AU - Meyer, Fredric B.

AU - Marsh, W. Richard

AU - Roche, Patrick

AU - Weigand, Stephen D.

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N2 - Object. The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods. The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures - that is, staining intensity, percentage of positively stained cells, and immunoreactive score - Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p <0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p <0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions. The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.

AB - Object. The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods. The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures - that is, staining intensity, percentage of positively stained cells, and immunoreactive score - Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p <0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p <0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions. The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.

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