Ischemia induced changes in expression of the astrocyte glutamate transporter GLT1 in hippocampus of the rat.
Changes in cellular uptake of glutamate following transient cerebral ischemia is of possible importance to ischemia induced cell death. In the present study, we employed in situ hybridization and immunohistochemistry to investigate the influence of cerebral ischemia on expression of mRNA and protein of the astrocyte glutamate transporter GLT1, and of glial fibrillary acidic protein. Different subfields of CA1 and CA3 of the rat hippocampus were studied at various time-points after ischemia (days 1, 2, 4, and 21). In CA1, GLT1-mRNA was decreased at all time-points after ischemia except from day 2, whereas in CA3, decreases were seen only on day 1. Expression of GLT1-protein in CA1 was unchanged during the initial days after ischemia, but decreased markedly from day 2 to 4. In CA3, GLT1-protein increased progressively throughout the observation period after ischemia. Following the degeneration of CA1 pyramidal cells, a positive correlation between the number of CA1 pyramidal cells and expression of either GLT1-mRNA or -protein was evident selectively in CA1. Increases in expression of mRNA and protein of glial fibrillary acidic protein were present from day 2, most notable in CA1. The present data provide evidence that expression of GLT1 in CA1 of the hippocampus is not decreased persistently before the degeneration of CA1 pyramidal cells, but is downregulated in response to loss of these neurons. Since the reduction in GLT1 expression evolved concomitantly with the degeneration of CA1 pyramidal cells, it may contribute to the severity of CA1 pyramidal cell loss. A progressive postischemic increase in GLT1 expression in CA3 may be linked to the resistance of CA3 neurons to ischemic cell damage.
Bruhn
T
T
Laboratory of Neuropathology, Institute of Molecular Pathology, University of Copenhagen, Denmark. tbr@nepa.ku.dk
Levy
L M
LM
Nielsen
M
M
Christensen
T
T
Johansen
F F
FF
Diemer
N H
NH
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger