title: Disturbance of hippocampal long-term potentiation after transient ischemia in GFAP deficient mice.
abstract: GFAP (glial fibrillary acidic protein) is an intermediate filament protein found exclusively in the astrocytes of the central nervous system. We studied the role of GFAP in the neuronal degeneration in the hippocampus after transient ischemia using knockout mice. Wild-type C57 Black/6 (GFAP(+/+)) mice and mutant (GFAP(-/-)) mice were subjected to occlusion of both carotid arteries for 5-15 min. Hippocampal slices were prepared 3 days after reperfusion and the field excitatory postsynaptic potentials (fEPSP) in the CA1 were recorded. High frequency stimulation induced robust long-term potentiation (LTP) in GFAP(-/-), as in GFAP(+/+) mice. After ischemia, however, the LTP in GFAP(-/-) was significantly depressed. Similarly, paired pulse facilitation (PPF) displayed little difference between GFAP(+/+) and GFAP(-/-), but after ischemia, the PPF in GFAP(-/-) showed a depression. Histological study revealed that loss of CA1 and CA3 pyramidal neurons after ischemia was marked in GFAP(-/-). MAP2 (dendritic) immunostaining in the post-ischemic hippocampus showed little difference but NF200 (axonal) immunoreactivity was reduced in GFAP(-/-). S100beta (glial) immunoreactivity was similar in the post-ischemic hippocampus of the GFAP(+/+) and GFAP(-/-), indicating that reactive astrocytosis did not require GFAP. Our results suggest that GFAP has an important role in astrocyte-neural interactions and that ischemic insult impairs LTP and accelerates neuronal death.
authors.affiliation: Department of Surgical Neurology, Jichi Medical School, Tochigi, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Katoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Oguro
authors.forename: Kuniko
authors.initials: K
authors.lastname: Shimazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Gomi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Toshio
authors.initials: T
authors.lastname: Masuzawa
authors.forename: Nobufumi
authors.initials: N
authors.lastname: Kawai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins