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Tissue inhibitor of metalloproteinases-1 (TIMP-1) is differentially induced in neurons and astrocytes after seizures: evidence for developmental, immediate early gene, and lesion response.

Rivera, Santiago, Tremblay, Evelyne, Timsit, Serge, Canals, Oriol, Ben-Ari, Yezekiel, Khrestchatisky, Michel·1997·The Journal of Neuroscience
DOI 10.1523/jneurosci.17-11-04223.1997
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Abstract

We investigated in vivo the expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in the rat CNS after kainate (KA)-induced excitotoxic seizures.In situ hybridization revealed that TIMP-1 mRNA is induced rapidly and massively in most regions of the adult forebrain after KA treatment. Neuronal activity seems to be necessary but not sufficient to trigger TIMP-1 induction, because it is not observed in seizing 10-d-old pups, unlike what is observed in 21- and 35-d-old animals after seizures. The rapid induction of TIMP-1 is not prevented by the inhibitor of protein synthesis cycloheximide, suggesting that, after seizures, TIMP-1 is induced in neurons as an immediate early gene (IEG). The initial neuronal upregulation is followed by enhanced expression in astrocytes, as assessed by double-labeling experiments. In the hippocampus rapid increases in mRNA are followed by relatively delayed (8 hr after KA) increases in TIMP-1 immunoreactivity in the perisomatic and dendro–axonic areas, suggesting secretion of the protein. At 3 d after KA treatment, strong immunoreactivity is found in astrocytes and in the cell bodies and dendro–axonic projections of resistant neurons such as the dentate granule cells. Taken together, the results suggest that TIMP-1 may be instrumental for neurons and astrocytes in coupling early cellular events triggered by seizures with the regulation of long-lasting changes involved in tissue reorganization and/or neuroprotection.

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Metadata

Authors
Rivera, S., Tremblay, E., Timsit, S., Canals, O., Ben-Ari, Y., & Khrestchatisky, M.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1997-06-01
Volume
17
Issue
11
Pages
4223-4235
ISSN
  • 0270-6474
  • 1529-2401
DOI
10.1523/jneurosci.17-11-04223.1997
Cited by
135
References
0
Language
en
Licence
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)

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