Loss of astrocytic domain organization in the epileptic brain.

Full 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.

Author information

Author/s: Oberheim, Nancy Ann (NA); Tian, Guo-Feng (GF); Han, Xiaoning (X); Peng, Weiguo (W); Takano, Takahiro (T); Ransom, Bruce (B); Nedergaard, Maiken (M);

Affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA.

Grants: NS030007 (Agency:NINDS NIH HHS) ; NS038073 (Agency:NINDS NIH HHS) ; NS50315 (Agency:NINDS NIH HHS) ; T32 GM07356 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2008-Mar; vol 28 (issue 13) : pp 3264-76

Dates: Created 2008/03/27; Completed 2008/04/28;

PMID: 18367594, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amino Acids - diagnostic use
Amyloid beta-Protein Precursor - genetics; metabolism
Animals
Anticonvulsants - therapeutic use
Astrocytes - drug effects; physiology
Basic Helix-Loop-Helix Transcription Factors - genetics; metabolism
Behavior, Animal
Brain - drug effects; pathology; physiopathology
Dendrites - pathology
Disease Models, Animal
Electroencephalography - methods

Epilepsy - chemically induced; drug therapy; genetics; pathology
Gene Expression Regulation - physiology
Glial Fibrillary Acidic Protein - genetics; metabolism
Kainic Acid
Luminescent Proteins - genetics; metabolism
Mice
Mice, Transgenic
Nerve Tissue Proteins - metabolism
Neurons - metabolism
Time Factors
Valproic Acid - therapeutic use

Associated Chemicals: Amino Acids (0) ; Amyloid beta-Protein Precursor (0) ; Anticonvulsants (0) ; Basic Helix-Loop-Helix Transcription Factors (0) ; Glial Fibrillary Acidic Protein (0) ; Hand1 protein, mouse (0) ; Luminescent Proteins (0) ; Nerve Tissue Proteins (0) ; dolaisoleucine (0) ; yellow fluorescent protein, mouse (0) ; Kainic Acid (487-79-6) ; Valproic Acid (99-66-1)

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