Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors
| Autor: | Mirna Kvajo, Carl C.H. Petersen, Ulrich Hengst, Edgardo Troncoso, Sandrine Lefort, Hugo Albrecht, Denis Monard, Jozsef Zoltan Kiss, Marita Meins |
|---|---|
| Předmět: |
Nervous system
Male medicine.medical_treatment Synaptic Transmission Peptide Hydrolases/ metabolism Serine Amyloid beta-Protein Precursor Mice Genes Reporter Neural Pathways Premovement neuronal activity Receptors N-Methyl-D-Aspartate/ physiology Mice Knockout Neuronal Plasticity biology General Neuroscience Vibrissae/physiology Brain Neuronal Plasticity/ physiology medicine.anatomical_structure Gene Expression Regulation Enzymologic/physiology Somatosensory Cortex/physiology NMDA receptor Female Proteases Recombinant Fusion Proteins Development/Plasticity/Repair Sensation Receptors Cell Surface Receptors Cell Surface/genetics/ physiology Receptors N-Methyl-D-Aspartate Gene Expression Regulation Enzymologic Neural Pathways/physiology Evoked Potentials Somatosensory medicine Animals Brain/ enzymology/ physiology Beta-Galactosidase/genetics Sensation/physiology Serine protease Protease Somatosensory Cortex Barrel cortex Evoked Potentials Somatosensory/physiology beta-Galactosidase ddc:616.8 Protease Nexins Mice Inbred C57BL Synaptic Transmission/physiology Vibrissae biology.protein Amyloid beta-Protein Precursor/genetics/ physiology Neuroscience Peptide Hydrolases |
| Zdroj: | Journal of Neuroscience, Vol. 24, No 43 (2004) pp. 9734-9743 |
| ISSN: | 0270-6474 |
| Popis: | Serine proteases are considered to be involved in plasticity-related events in the nervous system, but theirin vivotargets 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 thein vivofunction of the NMDA receptors and the proper function of sensory pathways. |
| Databáze: | OpenAIRE |
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