Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons
| Autor: | Nicole Schaeren-Wiemers, Petra Piosik, Stefania Franzoni, Marita Meins, Edgardo Troncoso, Denis Monard, Jozsef Zoltan Kiss, Christian Brösamle, Zoltán Molnár, Martin E. Schwab |
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| Předmět: |
Carrier Proteins/ biosynthesis/genetics
Male Evoked Potentials/genetics Motor Activity/genetics medicine.medical_treatment Receptor Nerve Growth Factor Weight Loss/genetics Amyloid beta-Protein Precursor Mice Serpin E2 Gliosis Evoked Potentials Muscular Atrophy/genetics/pathology Motor Neurons Protease Nexins Behavior Animal General Neuroscience Pyramidal Cells Receptors Nerve Growth Factor/metabolism Brain Electroencephalography Survival Rate Muscular Atrophy medicine.anatomical_structure Gliosis/pathology Spinal Cord Brain/metabolism/pathology Disease Progression Female medicine.symptom Genetically modified mouse Proteases Programmed cell death Serine Proteinase Inhibitors Motor Neuron Disease/diagnosis/ enzymology/ genetics/pathology Pyramidal Cells/ metabolism/pathology Mice Transgenic Receptors Cell Surface Receptors Nerve Growth Factor Biology Neurotransmission Motor Activity Mice Neurologic Mutants Weight Loss medicine Animals Serine Proteinase Inhibitors/biosynthesis/genetics ARTICLE Motor Neuron Disease Protease Motor Neurons/ metabolism/pathology Motor neuron Axons ddc:616.8 Spinal Cord/metabolism/pathology Mice Inbred C57BL Axons/pathology Carrier Proteins Neuroscience |
| Zdroj: | Europe PubMed Central Journal of Neuroscience, Vol. 21, No 22 (2001) pp. 8830-8841 Scopus-Elsevier |
| ISSN: | 0270-6474 |
| Popis: | Perturbation of the homeostasis between proteases and their inhibitors has been associated with lesion-induced or degenerative neuronal changes. Protease nexin-1 (PN-1), a secreted serine protease inhibitor, is constitutively expressed in distinct neuronal cell populations of the adult CNS. In an earlier study we showed that transgenic mice with ectopic or increased expression of PN-1 in postnatal neurons have altered synaptic transmission. Here these mice are used to examine the impact of an extracellular proteolytic imbalance on long-term neuronal function. These mice develop disturbances in motor behavior from 12 weeks on, with some of the histopathological changes described in early stages of human motor neuron disease, and neurogenic muscle atrophy in old age. In addition, sensorimotor integration, measured by epicranial multichannel recording of sensory evoked potentials, is impaired. Our results suggest that axonal dysfunction rather than cell death underlies these phenotypes. In particular, long projecting neurons, namely cortical layer V pyramidal and spinal motor neurons, show an age-dependent vulnerability to PN-1 overexpression. These mice can serve to study early stages ofin vivoneuronal dysfunction not yet associated with cell loss. |
| Databáze: | OpenAIRE |
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