title: Loss of astrocytic domain organization in the epileptic brain.
abstract: Gliosis is a pathological hallmark of posttraumatic epileptic foci, but little is known about these reactive astrocytes beyond their high glial fibrillary acidic protein (GFAP) expression. Using diolistic labeling, we show that cortical astrocytes lost their nonoverlapping domain organization in three mouse models of epilepsy: posttraumatic injury, genetic susceptibility, and systemic kainate exposure. Neighboring astrocytes in epileptic mice showed a 10-fold increase in overlap of processes. Concurrently, spine density was increased on dendrites of excitatory neurons. Suppression of seizures by the common antiepileptic, valproate, reduced the overlap of astrocytic processes. Astrocytic domain organization was also preserved in APP transgenic mice expressing a mutant variant of human amyloid precursor protein despite a marked upregulation of GFAP. Our data suggest that loss of astrocytic domains was not universally associated with gliosis, but restricted to seizure pathologies. Reorganization of astrocytes may, in concert with dendritic sprouting and new synapse formation, form the structural basis for recurrent excitation in the epileptic brain.
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors: Nancy Ann
authors: NA
authors: Oberheim
authors: Guo-Feng
authors: GF
authors: Tian
authors: Xiaoning
authors: X
authors: Han
authors: Weiguo
authors: W
authors: Peng
authors: Takahiro
authors: T
authors: Takano
authors: Bruce
authors: B
authors: Ransom
authors: Maiken
authors: M
authors: Nedergaard
mesh_terms: D000596:Amino Acids; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D003712:Dendrites / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013997:Time Factors; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D016564:Amyloid beta-Protein Precursor; D000927:Anticonvulsants; D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D007608:Kainic Acid; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D014635:Valproic Acid; C095572:Hand1 protein, mouse; C098463:dolaisoleucine