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.
MeSH terms
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Amyloid beta-Protein Precursor
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Animals
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Epilepsy / genetics
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Epilepsy / physiopathology*
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Hippocampus / physiology*
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Hippocampus / physiopathology
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Kinetics
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Long-Term Potentiation*
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Mice
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Mice, Knockout
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Mice, Neurologic Mutants
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Mice, Transgenic
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Neurons / physiology*
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Promoter Regions, Genetic
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Protease Nexins
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Receptors, Cell Surface
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Recombinant Fusion Proteins / biosynthesis
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Serine Proteinase Inhibitors / genetics
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Serine Proteinase Inhibitors / physiology
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Synaptic Transmission
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Thy-1 Antigens / biosynthesis
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Thy-1 Antigens / genetics
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Time Factors
Substances
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Amyloid beta-Protein Precursor
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Carrier Proteins
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Protease Nexins
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Serine Proteinase Inhibitors
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Thy-1 Antigens