Degeneration and proliferation of astrocytes in the mouse dentate gyrus after pilocarpine-induced status epilepticus.
Astrocytes are relatively resistant to injury compared to neurons and oligodendrocytes. Here, we report transient region-specific loss of astrocytes in mice early after pilocarpine-induced status epilepticus (SE). In the dentate hilus, immunoreactivity for glial acidic fibrillary protein (GFAP) was decreased, and the number of healthy appearing GFAP- or S100beta-positive cells was significantly reduced (> or =65%) 1 and 3 days after pilocarpine-induced SE. Many remaining GFAP-positive cells were shrunken, and 1 day after SE electron microscopy revealed numerous electron-dense degenerating astrocyte processes and degenerating glial somata in the hilus. Degeneration of GFAP-expressing cells may be linked to hilar neuronal death, because we did not observe loss of astrocytes after kainate-induced SE, after which hilar neurons remained intact. Ten days after SE, hilar GFAP immunoreactivity had returned, partially from GFAP-positive cells in the hilus. Unlike control mice, many GFAP-positive hilar processes originated from cell bodies located in the subgranular zone (SGZ). To investigate whether proliferation contributes to hilar repopulation, we injected 5-bromo-2'-deoxyuridine (BrdU) 3 days after SE. Five hours later and up to 31 days after SE, many BrdU/GFAP colabeled cells were found in the hilus and the SGZ, some with hilar processes, indicating that proliferation in both areas contributes to generation of hilar astrocytes and astrocyte processes. In contrast to pilocarpine-induced SE in mice, astrocyte degeneration was not found after pilocarpine-induced SE in rats. These findings demonstrate astrocyte degeneration in the mouse dentate hilus specifically in the mouse pilocarpine epilepsy model, followed by astrogenesis leading to hilar repopulation.
Borges
Karin
K
Department of Pharmacology, Emory University, Atlanta, GA 30322, USA. karin.borges@ttuhsc.edu
McDermott
Dayna
D
Irier
Hasan
H
Smith
Yoland
Y
Dingledine
Raymond
R
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000166:cytology / Q000502:physiology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D010862:Pilocarpine