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Title

Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors

Authors
Kvajo, Mirna
Albrecht, Hugo
Meins, Marita
Hengst, Ulrich
Troncoso, Edgardo
Lefort, Sandrine
Petersen, C. C.
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Published in Journal of Neuroscience. 2004, vol. 24, no. 43, p. 9734-9743
Abstract Serine proteases are considered to be involved in plasticity-related events in the nervous system, but their in vivo targets and the importance of their control by endogenous inhibitors are still not clarified. Here, we demonstrate the crucial role of a potent serine protease inhibitor, protease nexin-1 (PN-1), in the regulation of activity-dependent brain proteolytic activity and the functioning of sensory pathways. Neuronal activity regulates the expression of PN-1, which in turn controls brain proteolytic activity. In PN-1-/- mice, absence of PN-1 leads to increased brain proteolytic activity, which is correlated with an activity-dependent decrease in the NR1 subunit of the NMDA receptor. Correspondingly, reduced NMDA receptor signaling is detected in their barrel cortex. This is coupled to decreased sensory evoked potentials in the barrel cortex and impaired whisker-dependent sensory motor function. Thus, a tight control of serine protease activity is critical for the in vivo function of the NMDA receptors and the proper function of sensory pathways.
Keywords Amyloid beta-Protein Precursor/genetics/ physiologyAnimalsBrain/ enzymology/ physiologyEvoked Potentials, Somatosensory/physiologyFemaleGene Expression Regulation, Enzymologic/physiologyGenes, ReporterMaleMiceMice, Inbred C57BLMice, KnockoutNeural Pathways/physiologyNeuronal Plasticity/ physiologyPeptide Hydrolases/ metabolismReceptors, Cell Surface/genetics/ physiologyReceptors, N-Methyl-D-Aspartate/ physiologyRecombinant Fusion ProteinsSensation/physiologySomatosensory Cortex/physiologySynaptic Transmission/physiologyVibrissae/physiologyBeta-Galactosidase/genetics
Stable URL http://archive-ouverte.unige.ch/unige:10330
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Other version: http://www.jneurosci.org/cgi/reprint/24/43/9734.pdf
Identifiers
PMID: 15509762
Structures
Research group Progéniteurs neuronaux
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