Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator

Stella E. Tsirka, Anna Gualandris, David G Amaral, Sidney Strickland

Research output: Contribution to journalArticle

566 Citations (Scopus)

Abstract

NEURONAL degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced1,2. The activity of tPA in neural tissue is correlated with neurite outgrowth3, regeneration4 and migration5, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.

Original languageEnglish (US)
Pages (from-to)341-344
Number of pages4
JournalNature
Volume377
Issue number6547
StatePublished - Sep 28 1995
Externally publishedYes

Fingerprint

Neurotoxins
Tissue Plasminogen Activator
Seizures
Hippocampus
Neuronal Plasticity
Plasminogen
Fibrinolysin
Microglia
Serine Proteases
Neurites
Brain Ischemia
Epilepsy
Alzheimer Disease
Peptide Hydrolases
Brain

ASJC Scopus subject areas

  • General

Cite this

Tsirka, S. E., Gualandris, A., Amaral, D. G., & Strickland, S. (1995). Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature, 377(6547), 341-344.

Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. / Tsirka, Stella E.; Gualandris, Anna; Amaral, David G; Strickland, Sidney.

In: Nature, Vol. 377, No. 6547, 28.09.1995, p. 341-344.

Research output: Contribution to journalArticle

Tsirka, SE, Gualandris, A, Amaral, DG & Strickland, S 1995, 'Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator', Nature, vol. 377, no. 6547, pp. 341-344.
Tsirka, Stella E. ; Gualandris, Anna ; Amaral, David G ; Strickland, Sidney. / Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. In: Nature. 1995 ; Vol. 377, No. 6547. pp. 341-344.
@article{850d173d36374254901b4fe13a8b88b1,
title = "Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator",
abstract = "NEURONAL degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced1,2. The activity of tPA in neural tissue is correlated with neurite outgrowth3, regeneration4 and migration5, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.",
author = "Tsirka, {Stella E.} and Anna Gualandris and Amaral, {David G} and Sidney Strickland",
year = "1995",
month = "9",
day = "28",
language = "English (US)",
volume = "377",
pages = "341--344",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6547",

}

TY - JOUR

T1 - Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator

AU - Tsirka, Stella E.

AU - Gualandris, Anna

AU - Amaral, David G

AU - Strickland, Sidney

PY - 1995/9/28

Y1 - 1995/9/28

N2 - NEURONAL degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced1,2. The activity of tPA in neural tissue is correlated with neurite outgrowth3, regeneration4 and migration5, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.

AB - NEURONAL degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced1,2. The activity of tPA in neural tissue is correlated with neurite outgrowth3, regeneration4 and migration5, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.

UR - http://www.scopus.com/inward/record.url?scp=0029088484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029088484&partnerID=8YFLogxK

M3 - Article

C2 - 7566088

AN - SCOPUS:0029088484

VL - 377

SP - 341

EP - 344

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6547

ER -