Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation |
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| Authors: | A Lüthi H Van der Putten FM Botteri IM Mansuy M Meins U Frey G Sansig C Portet M Schmutz M Schr?der C Nitsch JP Laurent D Monard |
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| Affiliation: | Pharma Division, Preclinical Research, F. Hoffmann-La Roche Limited, CH-4002 Basel, Switzerland. |
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| 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. |
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