Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation

Andreas Lüthi, Herman Van Der Putten, Florence M. Botteri, Isabelle M. Mansuy, Marita Meins, Uwe Frey, Gilles Sansig, Chantal Portet, Markus Schmutz, Markus Schröder, Cordula Nitsch, Jean Paul Laurent, Denis Monard

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146 Scopus citations

Abstract

Protease nexin-1 (PN-1), a member of the serpin superfamily, controls the activity of extracellular serine proteases and is expressed in the brain. Mutant mice overexpressing PN-1 in brain under the control of the Thy-1 promoter (Thy 1/PN-1) or lacking PN-1 (PN-1 -/-) were found to develop epileptic activity in vivo and in vitro. Theta burst-induced long-term potentiation (LTP) and NMDA receptor-mediated synaptic transmission in the CA1 field of hippocampal slices were augmented in Thy 1/PN-1 mice and reduced in PN-1-/mice. Compensatory changes in GABA-mediated inhibition in Thy 1/PN- 1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic transmission.

Original languageEnglish (US)
Pages (from-to)4688-4699
Number of pages12
JournalJournal of Neuroscience
Volume17
Issue number12
DOIs
StatePublished - 1997

Keywords

  • Epileptiform activity
  • Knock-out and transgenic mice
  • Long-term potentiation
  • Protease modulation
  • Protease nexin-1
  • Synaptical activity

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lüthi, A., Van Der Putten, H., Botteri, F. M., Mansuy, I. M., Meins, M., Frey, U., Sansig, G., Portet, C., Schmutz, M., Schröder, M., Nitsch, C., Laurent, J. P., & Monard, D. (1997). Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. Journal of Neuroscience, 17(12), 4688-4699. https://doi.org/10.1523/jneurosci.17-12-04688.1997