Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic Neurons

Marita Meins, Petra Piosik, Nicole Schaeren-Wiemers, Stefania Franzoni, Edgardo Troncoso, J. Kiss, Christian Brösamle, Martin E. Schwab, Zoltán Molnár, Denis Monard

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 of in vivo neuronal dysfunction not yet associated with cell loss.

Original languageEnglish
Pages (from-to)8830-8841
Number of pages12
JournalJournal of Neuroscience
Volume21
Issue number22
Publication statusPublished - Nov 15 2001

Fingerprint

Protease Nexins
Serine Proteinase Inhibitors
Neurons
Motor Neuron Disease
Muscular Atrophy
Motor Neurons
Protease Inhibitors
Evoked Potentials
Synaptic Transmission
Transgenic Mice
Homeostasis
Cell Death
Phenotype
Population

Keywords

  • Axonopathy
  • Layer V pyramidal cells
  • Motor behavior
  • Motor neuron disease
  • Muscle atrophy
  • PN-1
  • Proteolytic inhibition
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Meins, M., Piosik, P., Schaeren-Wiemers, N., Franzoni, S., Troncoso, E., Kiss, J., ... Monard, D. (2001). Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic Neurons. Journal of Neuroscience, 21(22), 8830-8841.

Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic Neurons. / Meins, Marita; Piosik, Petra; Schaeren-Wiemers, Nicole; Franzoni, Stefania; Troncoso, Edgardo; Kiss, J.; Brösamle, Christian; Schwab, Martin E.; Molnár, Zoltán; Monard, Denis.

In: Journal of Neuroscience, Vol. 21, No. 22, 15.11.2001, p. 8830-8841.

Research output: Contribution to journalArticle

Meins, M, Piosik, P, Schaeren-Wiemers, N, Franzoni, S, Troncoso, E, Kiss, J, Brösamle, C, Schwab, ME, Molnár, Z & Monard, D 2001, 'Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic Neurons', Journal of Neuroscience, vol. 21, no. 22, pp. 8830-8841.
Meins, Marita ; Piosik, Petra ; Schaeren-Wiemers, Nicole ; Franzoni, Stefania ; Troncoso, Edgardo ; Kiss, J. ; Brösamle, Christian ; Schwab, Martin E. ; Molnár, Zoltán ; Monard, Denis. / Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic Neurons. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 22. pp. 8830-8841.
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