Expression of connexin genes in hippocampus of kainate-treated and kindled rats under conditions of experimental epilepsy. Brain Res. Mol. Brain Res. 83:44-51

Abteilung für Molekulargenetik, Institut für Genetik, Universität Bonn, 53117 Bonn, Germany
Molecular Brain Research (Impact Factor: 2). 12/2000; 83(1-2):44-51. DOI: 10.1016/S0169-328X(00)00195-9
Source: PubMed


We have analyzed whether the expression of connexin genes is altered in the hippocampus of kindled and kainate-treated rats, i.e., animal models of human temporal lobe epilepsy. We have tested this hypothesis by analyzing mRNA, protein abundance and cellular location of connexins (Cx) 43, 36, 32 and 30. The expression of glial fibrillary acid protein and mRNA was also monitored both in kainate-treated and kindled rats, in order to take into account reactive gliosis under these conditions. We found significantly increased expression of GFAP mRNA (100%) and protein (178%) in kainate-treated rats 4 weeks after kainate application, whereas in kindled rats only moderate increases of GFAP mRNA and protein were detected 2–3 weeks (group 2) or 4–6 weeks (group 1) after the last stage 5 induced seizure. Under gliotic conditions, connexins 43 and 30 mRNA or protein expression in astrocytes of kainate-treated rats were nearly unaffected. Cx36 mRNA expression (presumably in neurons) was significantly reduced (44%), whereas abundance of Cx36 protein was only slightly reduced. In both groups of kindled rats, Cx30 and Cx43 mRNA or protein expression were either slightly decreased or unchanged. Again, Cx36 mRNA and protein expression were reduced by about half in group 2. Immunofluorescence analysis of Cx43, Cx36 and Cx30 expression revealed that 4 weeks after the last kainate administration or kindling, cellular localization of these connexins was indistinguishable from control animals.

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Available from: Rafael Gutiérrez
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    • "Cx36 Principal cells Condorelli et al. (1998, 2000, 2003), Belluardo et al. (2000), Zoidl et al. (2002), Weickert et al. (2005) and Nagy (2012) Interneurons Kosaka and Hama (1985), Freund and Buzsáki (1996), Condorelli et al. (2000) (2003) and Baude et al. (2007) Cx43 Astrocytes Söhl et al. (2000), Nagy et al. (2001), Ohsumi et al. (2010), Abbasian et al. (2012) and Sayyah et al. (2012) Cx45 Oligonendrocytes Kunzelmann et al. (1997) and Condorelli et al. (2003) Principal cells Maxeiner et al. (2003) and Weickert et al. (2005) Cx47 Oligonendrocytes Weickert et al. (2005) Principal cells Teubner et al. (2001) Panexins 1 Principal cells Bruzzone et al. (2003), Ray et al. (2005), Vogt et al. (2005), Weickert et al. (2005), Zappala et al. (2006) and Zoidl et al. (2007) Panexins 2 Principal cells Bruzzone et al. (2003) and Vogt et al. (2005) The relevance of GJs to brain functions is evident in early brain development. It was earlier shown that there are numerous GJs in immature brain tissue, which decline rapidly as maturation progresses (Peinado et al., 1993; Perez-Velazquez and Carlen, 2000; Yuste et al., 1995). "
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    ABSTRACT: Gap junctions (GJs) were discovered more than five decades ago, and since that time enormous strides have been made in understanding their structure and function. Despite the voluminous literature concerning the function of GJs, the involvement of these membrane structures in the central mechanisms underlying oscillations and synchrony in the neuronal network is still a matter of intensive debate. This review summarizes what is known concerning the involvement of GJs as electrical synapses in mechanisms underlying the generation of oscillations in theta band. The first part of the chapter discusses the role of GJs in mechanisms of oscillations and synchrony. Following this, in vitro, ex vivo, and in vivo experiments concerning the involvement of GJs in the generation of hippocampal formation theta in rats are reviewed.
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    • "In contrast to Cx43, Cx30 levels were extremely low in the cortical hemispheres of wild-type mice. This is consistent with the previous demonstration of high levels of Cx43 and much lower levels of Cx30 within hippocampal and neocortical tissue by other groups [3] [13] [21]. As expected, Cx30 expression was virtually absent in Cx30−/− mice (Fig. 1). "
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    ABSTRACT: The glial glutamate transporter subtypes, GLT-1/EAAT-2 and GLAST/EAAT-1 clear the bulk of extracellular glutamate and are severely dysregulated in various acute and chronic brain diseases. Despite the previous identification of several extracellular factors modulating glial glutamate transporter expression, our knowledge of the regulatory network controlling glial glutamate transport in health and disease still remains incomplete. In studies with cultured cortical astrocytes, we previously obtained evidence that glial glutamate transporter expression is also affected by gap junctions/connexins. To assess whether gap junctions would likewise control the in vivo expression of glial glutamate transporters, we have now assessed their expression levels in brains of conditional Cx43 knockout mice, total Cx30 knockouts, as well as Cx43/Cx30 double knockouts. We found that either knocking out Cx30, Cx43, or both increases GLT-1/EAAT-2 protein levels in the cerebral cortex to a similar extent. By contrast, GLAST/EAAT-1 protein levels maximally increased in cerebral cortices of Cx30/Cx43 double knockouts, implying that gap junctions differentially affect the expression of GLT-1/EAAT-2 and GLAST/EAAT-1. Quantitative PCR analysis further revealed that increases in glial glutamate transporter expression are brought about by transcriptional and translational/posttranslational processes. Moreover, GLT-1/EAAT-2- and GLAST/EAAT-1 protein levels remained unchanged in the hippocampi of Cx43/Cx30 double knockouts when compared to Cx43fl/fl controls, indicating brain region-specific effects of gap junctions on glial glutamate transport. Since astrocytic gap junction coupling is affected in various forms of brain injuries, our findings point to gap junctions/connexins as important regulators of glial glutamate turnover in the diseased cerebral cortex.
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    • ", reported no change in Cx43 mRNA expression in amygdala of the rats during development of amygdala kindling. Moreover, it has been found that hippocampal Cx43 expression at both mRNA and protein level is unchanged or slightly decreased in fully kindled rats 2–6 weeks after the last kindled seizures occurrence (Sohl et al., 2000 "
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    ABSTRACT: Identification of key molecular changes occurring during epileptogenesis provides better understanding of epilepsy and helps to develop strategies to modify those changes and thus, block the epileptogenic process. Gap junctional communication is thought to be involved in epileptogenesis. This communication can be affected by changes in expression of gap junctional protein subunits called connexins (Cxs). One of the main brain regions involved in epileptogenesis is the hippocampus in which there is a network of gap junctional communication between different cell types. Cx36 and Cx43 expressions at both mRNA and protein level were measured in rat hippocampus during epileptogenesis in the kindling model of epilepsy. Cx36 expression at both mRNA and protein level was upregulated during acquisition of focal seizures but returned to basal level after acquisition of secondarily-generalized seizures. No change in Cx43 gene and protein expression was found during kindling epileptogenesis. These results further point out the significance of Cx36 as a target to modify epileptogenic process and to develop antiepileptogenic treatments.
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