Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain
Julie E. SimpsonPaul G. InceG. LaceG. ForsterPamela J. ShawFiona E. MatthewsGeorge M. SavvaCarol BrayneStephen B. Wharton
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Abstract: The El (epileptic) mouse is considered a model for complex partial seizures in humans. Seizures in El mice begin around 7–8 weeks of age and persist throughout life. To determine if astrocytic gliosis was present in adult seizing El mice, the distribution of glial fibrillary acidic protein (GFAP) was studied in the hippocampus using an antibody to GFAP. The mean number of GFAP‐positive cells per square millimeter of hippocampus was approximately 15‐ to 40‐fold higher in adult El mice than in nonseizing control C57BL/ 6J (B6) mice or in young nonseizing El mice. Relative GFAP concentration (expressed per milligram of total tissue protein) in hippocampus and cerebellum was estimated by densitometric scanning of peroxidase‐stained western blots. GFAP concentration was 2.7‐fold greater in hippocampus of adult seizing El mice than in the control B6 mice. No differences in GFAP content were detected between the strains in the cerebellum. Because gangliosides can serve as cell surface markers for changes in neuronal cytoarchitecture, they were analyzed to determine if the gliotic response in El mice was associated with changes in neural composition. Although the total ganglioside concentration of hippocampus, cerebral cortex, and cerebellum was similar in adult El and control B6 mice, a synaptic membrane enriched ganglioside, GD1a, was elevated in the adult El cerebral cortex and hippocampus. The findings indicate that El mice express a type of gliosis that is not accompanied by obvious neuronal loss.
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Ganglioside
GFAP stain
Synapsin I
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We investigated the effects of ethanol exposure on the shape of the cell and the morphology of intermediate filaments (IF) of cortical astrocytes in primary culture. The content and distribution of glial fibrillary acidic protein (GFAP), the major component of glial IF, was assessed using an anti-GFAP monoclonal antibody and fluorescence scanning densitometry together with quantitative pre- and post-embedding immunogold electron microscopy. The astrocytes were from 21-day-old fetuses obtained from both control and chronic alcoholic rats and were cultured for 28 days in the absence or presence of ethanol (25 mM). The main findings were: (a) ethanol-exposed astrocytes failed to develop processes or to acquire a filamentous IF distribution pattern; (b) these cells showed less GFAP than astrocytes without alcohol; (c) ethanol interfered with the reorganization of the anti-GFAP binding sites from clustered to random; and (d) astrocytes from alcohol-exposed fetuses cultured in the absence of ethanol also showed these alterations, suggesting initial damage to astrocyte precursor cells. Since the glial filaments play a crucial role in creating a scaffolding that guides neuronal migration, the effect of ethanol on astrocyte IF may possibly be correlated with the mechanisms underlying mental retardation and motor dysfunction which are characteristics of fetal alcohol syndrome.
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Neuroglia
Immunofluorescence
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Previous studies of human hepatic encephalopathy (HE) have shown decreased levels of glial fibrillary acidic protein (GFAP) in Alzheimer type II astrocytes. In view of the important role of ammonia in the pathogenesis of HE, we carried out immunocytochemical and enzyme-linked immunosorbent assay (ELISA) studies on the effect of ammonium chloride (10 mM) on GFAP content in primary astrocyte cultures. There was a 39% loss of GFAP after a four day treatment. There was no fall in total cell protein. Potential mechanisms for this apparent selective loss of GFAP are discussed.
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Neuroglia
Pathogenesis
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AIM: To observe the activity and distribution of astrocytes and glial fibrillary acid protein(GFAP) after middle cerebral artery occlusion (MCAO). METHODS: The rat MCAO model was made by two-kidney, tow clip renovascular hypertensive rat stroke prone(RHRSP). Rats were killed and brain samples were collected at the end of 1,3,6 and 9 weeks after MCAO, respectively. The ultrastructure of astrocytes was determined at broder of infarct (A area); distant of infarct (B area) and opposite of hemisphere (C area) by electron microscope. The number and optical density of GFAP-positive cells were also observed. RESULTS: The astrocyte proliferation distributed in the whole brain after MCAO. The highest numbers of GFAP-positive cells were observed at A area, then B area. The lowest numbers of GFAP positive cells were found in C area. The time course of GFAP-positive cell change was that the highest number was observed at 1 week after MCAO, then decreased by time from 3, 6 weeks to 9 weeks. The optical density of GFAP-positive cells showed the same patterns. CONCLUSION: The correlation between astrocyte proliferation and tissue damage after MCAO can be estimated by GFAP expression. The astrocyte proliferation plays an important role in healing process after MCAO.
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Optical density
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Astrocytosis
GFAP stain
Neuroglia
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In the rat hippocampus and cortex, the transcription of glial fibrillary acidic protein (GFAP), an astrocyte intermediate filament protein, is inhibited by glucocorticoids. The present study examined the regulation of GFAP expression by glucocorticoids in astrocytes in vitro. Corticosterone (CORT) increased GFAP messenger RNA, protein, and transcription rates in cultured primary neonatal astrocytes, responses opposite the GFAP responses to CORT in vivo. The direction of GFAP regulation by corticosterone in vitro is reversed by coculture with neurons or by extended culture for 3 months. The switch in the direction of GFAP regulation by CORT during prolonged culture is associated with a 3-fold increased prevalence of type II glucocorticoid receptor (GR). These findings were corroborated with a promoter construct that contained 1.9 kilobases of 5'-up-stream rat GFAP DNA with a luciferase reporter. Thus, the direction of GFAP transcription to CORT is subject to the postreplicative time in culture and to interactions with neurons, in which 5'-up-stream sequences contain sufficient information to mediate the switch in the direction of the response to CORT. This in vitro model may be used to analyze how interactions of astrocytes with neurons or other cell types influence the hormonal regulation of GFAP.
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Objective:To study the effects of cycolsporin A(CsA) on glial fibrillary acidic protein(GFAP) expression in hippocampal astrocytes of chronic kindling rats induced by pentylenetrazol(PTZ) and observe the change of the rat behavior.Methods:Seventy-two healthy Wistar rats were randomized into three equal groups,Group N,Group P and Group C.Group P and Group C were injected with 35mg/kg PTZ by intraperitoneal every day;Group C was injected with 10mg/kg CsA by vena caudalis every three days.The GFAP expression was determined by immunohistochemical technique in the hippocampi of the rats of each group at 4,7 and 14 days.Results:The reactive gliosis in the hippocamus was found before the occurrence of PTZ-induced seizure in the Group P,significantly different from those in the Group N and Group C(P0.01);the reactive gliosis in the Group C was less than that of Group P,significantly different from those in the Group N(P0.05).Conclusion:In the process of chronic kindling induced by PTZ,the GFAP expression in the hippocampal is gradually increased,finally inducing epileptogenesis;CsA can reduce gliosis in the hippocamus,and therefore,CsA can prevent epileptogenesis.
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In the prion diseases, extensive reactive gliosis is often found to be out of proportion to the degree of apparent neuronal damage.To evaluate the role of astrocytic gliosis in experimental scrapie of the mouse, we inoculated mice deficient in apolipoprotein E (apoE) or the glial fibrillary acidic protein (GFAP) with mouse prions. The expression of both apoE and GFAP in astrocytes increases as part of the reactive gliosis that accompanies scrapie. Null mice deficient in either apoE or GFAP inoculated with prions exhibited incubation times indistinguishable from untargeted control mice. The level of PrPSc and its regional deposition in the brains of ill mice deficient in either protein were also similar to control mice. Our findings demonstrate that neither apoE nor GFAP participates in the pathogenesis of the disease or in the production of PrPSc. NEUROLOGY 1996;47: 449-453
Gliosis
Apolipoprotein E
Pathogenesis
Neuroglia
Slow virus
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GFAP stain
Neurotoxicity
Neuroglia
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GFAP stain
Cloning (programming)
Trypsinization
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