The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate.
J Cell Biol
; 148(6): 1295-304, 2000 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-10725341
ABSTRACT
Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasminogênio
/
Proteoglicanas de Sulfatos de Condroitina
/
Convulsões
/
Neuritos
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Ativador de Plasminogênio Tecidual
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Fibrinolisina
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Hipocampo
/
Fibras Nervosas
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos