Related Experiment Videos
Serine protease inhibitor Spi2 mediated apoptosis of olfactory neurons
1Laboratoire Apoptose et Différenciation-Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, France.
Abstract:
The olfactory epithelium of adult mouse, where primary sensory neurons are massively committed to apoptosis by removal of their synaptic target, was used as a model to determine in vivo mechanisms for neuronal cell death induction. A macro-array assay revealed that the death of olfactory neurons is accompanied with over-expression of the serine protease inhibitor Spi2. This over-expression is associated with decreased serine protease activity in the olfactory mucosa. Moreover, in vitro or in vivo inhibition of serine proteases induced apoptotic death of olfactory neuronal cells. Interestingly, Spi2 over-expression is not occurring in olfactory neurons but in cells of the lamina propria, suggesting that Spi2 may act extracellularly as a cell death inducer. In that sense, we present evidence that in vitro Spi2 overexpression generates a secreted signal for olfactory neuron death. Hence, taken together these results document a possible novel mechanism for apoptosis induction that might occur in response to neurodegenerative insults.
Insights
Overexpression of serine protease inhibitor 2 (Spi2) in the olfactory epithelium induces neuronal apoptosis. This suggests a novel extracellular mechanism for cell death in neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Olfactory sensory neurons undergo massive apoptosis when their synaptic targets are removed.
- Understanding the in vivo mechanisms of neuronal cell death is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the in vivo mechanisms of neuronal cell death induction in the adult mouse olfactory epithelium.
- To identify molecular players involved in olfactory neuron apoptosis.
Main Methods:
- Utilized a macro-array assay to analyze gene expression changes during olfactory neuron death.
- Performed in vitro and in vivo experiments inhibiting serine proteases.
- Investigated the localization and function of serine protease inhibitor 2 (Spi2).
Main Results:
- Olfactory neuron apoptosis correlated with Spi2 overexpression and decreased serine protease activity.
- Inhibition of serine proteases induced apoptotic death in olfactory neurons.
- Spi2 overexpression, localized to lamina propria cells, secreted a signal inducing olfactory neuron death.
Conclusions:
- Spi2 acts as an extracellular inducer of olfactory neuron apoptosis.
- This study presents a novel mechanism for apoptosis induction potentially relevant to neurodegenerative insults.
- The findings highlight a new pathway for neuronal cell death in the nervous system.