Structural remodeling of fibrous astrocytes after axonal injury.
Reactive astrocytes are a pathological hallmark of many CNS injuries and neurodegenerations. They are characterized by hypertrophy of the soma and processes and an increase in the expression of glial fibrillary acidic protein. Because the cells obscure each other in immunostaining, little is known about the behavior of a single reactive astrocyte, nor how single astrocytes combine to form the glial scar. We have investigated the reaction of fibrous astrocytes to axonal degeneration using a transgenic mouse strain expressing enhanced green fluorescent protein in small subsets of astrocytes. Fibrous astrocytes in the optic nerve and corpus callosum initially react to injury by hypertrophy of the soma and processes. They retract their primary processes, simplifying their shape and dramatically reducing their spatial coverage. At 3 d after crush, quantitative analysis revealed nearly a twofold increase in the thickness of the primary processes, a halving of the number of primary processes leaving the soma and an eightfold reduction in the spatial coverage. In the subsequent week, they partially reextend long processes, returning to a near-normal morphology and an extensive spatial overlap. The resulting glial scar consists of an irregular array of astrocyte processes, contrasting with their original orderly arrangement. These changes are in distinct contrast to those reported for reactive protoplasmic astrocytes of the gray matter, in which the number of processes and branchings increase, but the cells continue to maintain nonoverlapping individual territories throughout their response to injury.
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. daniel_sun@meei.harvard.edu
Daniel
D
Sun
Ming
M
Lye-Barthel
Richard H
RH
Masland
Tatjana C
TC
Jakobs
D000818:Animals; D000963:Antimetabolites; D001253:Astrocytes / Q000473:pathology* / Q000648:ultrastructure; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D019470:Biolistics; D001973:Bromodeoxyuridine; D003337:Corpus Callosum / Q000293:injuries / Q000473:pathology; D003593:Cytoplasm / Q000473:pathology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009409:Nerve Crush; D009900:Optic Nerve / Q000473:pathology / Q000648:ultrastructure; D020221:Optic Nerve Injuries / Q000473:pathology
D000963:Antimetabolites; D005904:Glial Fibrillary Acidic Protein; D001973:Bromodeoxyuridine