title: Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy.
abstract: Following brain injury, and during the process of neurodegeneration, a reactive astrocytic proliferation occurs. This is accompanied by an increase in the synthesis of neuropeptides, cytokines, growth factors and glial fibrillary acidic protein (GFAP), a cell-specific marker for reactive astrocytes. Astrocytes are extensively coupled by gap junctions of the Cx43 connexin subtype. Several studies have shown that in severe trauma, coupling between astrocytes may add to the spread of the damaged area. In this study we ask whether the astrocytosis which is a feature of other neurodegenerative diseases also occurs in mesial temporal lobe epilepsy (MTLE) and whether it is accompanied by an increase in astrocytic communication through an upregulation of Cx43 gap junction channel proteins. In order to examine the astrocytic response and the expression pattern of Cx43 protein, double immunohistochemical labeling studies were undertaken using antibodies against GFAP and Cx43 applied to human hippocampal tissue resected from patients with MTLE, and to normal human control hippocampal tissue. Immunofluorescent labeling of astrocytes and Cx43 was examined using confocal laser scanning microscopy. The images obtained were quantitatively analysed and reconstructed using three-dimensional volume rendering. The results of this study have established that not only is astrocytosis greater in MTLE-affected tissues than previously suggested, but it is accompanied by a highly significant increase in astrocytic Cx43 protein levels. We hypothesize that this surprisingly large upregulation in Cx43 may exacerbate generalized seizures in the progression of MTLE.
authors.affiliation: Department of Anatomy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Carissa G
authors.initials: CG
authors.lastname: Fonseca
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
authors.forename: Louise F B
authors.initials: LF
authors.lastname: Nicholson
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D018031:Connexin 43 / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000378:metabolism* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D018613:Microscopy, Confocal; D051381:Rats; D012640:Seizures / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein