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Pronounced increase in prolyl endopeptidase activity in primary cultures of rat cerebral cortex during neuronal
A E Szappanos1, V Lakics, S L Erdö
1CNS Pharmacology Laboratory, Chinoin Co. Ltd., Budapest, Hungary.
Insights
Prolyl endopeptidase (PEP) activity significantly increases during early rat cerebral cortex development in vitro. Most PEP activity is found in glutamate-sensitive neurons, suggesting a role in neuronal differentiation.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- Prolyl endopeptidase (PEP) is a cytosolic serine protease.
- Neuronal differentiation involves complex molecular events.
- The role of PEP in brain development is not fully understood.
Purpose of the Study:
- To investigate the activity and localization of PEP during rat cerebral cortex development in vitro.
- To determine the potential role of PEP in neuronal differentiation.
Main Methods:
- Primary cultures of rat cerebral cortex were established and maintained for 16 days in vitro.
- PEP specific activity was measured at different developmental time points.
- Excitotoxic lesions were used to assess the cellular localization of PEP activity.
Main Results:
- PEP specific activity increased approximately 5-fold by day 7 of culture, coinciding with significant neuronal differentiation.
- PEP activity showed a slight increase during the second week of culture.
- Over 70% of PEP activity was localized in glutamate-sensitive neurons in mature cultures.
Conclusions:
- PEP activity is dynamically regulated during early cerebral cortex development.
- The localization of PEP in glutamate-sensitive neurons suggests a specific role in neuronal function.
- Findings indicate that prolyl endopeptidase may play a significant role in neuronal differentiation.
Abstract:
The activity of prolyl endopeptidase (PEP), a cytosolic serine protease, was examined in developing primary cultures of the rat cerebral cortex between days 1 and 16, in vitro. Cells underwent remarkable differentiation during the first week in culture, as indicated by the formation of clusters and by the rapid development and fasciculation of neurites. The specific activity of PEP showed a rapid, about 5-fold increase by day 7. The morphology of cultures remained nearly unchanged and the activity of PEP slightly increased during the second week. Excitotoxic lesion of the neuronal component of mature cultures revealed that the majority (over 70%) of PEP activity is localised in glutamate-sensitive neurons. Our findings indicate that PEP may play some role during neuronal differentiation.