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Phosphodiesterase 2 Inhibitors Promote Axonal Outgrowth in Organotypic Slice Co-Cultures
- Source :
- Neurosignals, Vol 21, Iss 3-4, Pp 197-212 (2012)
- Publication Year :
- 2013
- Publisher :
- S. Karger AG, 2013.
-
Abstract
- The development of appropriate models assessing the potential of substances for regeneration of neuronal circuits is of great importance. Here, we present procedures to analyze effects of substances on fiber outgrowth based on organotypic slice co-cultures of the nigrostriatal dopaminergic system in combination with biocytin tracing and tyrosine hydroxylase labeling and subsequent automated image quantification. Selected phosphodiesterase inhibitors (PDE-Is) were studied to identify their potential growth-promoting capacities. Immunohistochemical methods were used to visualize developing fibers in the border region between ventral tegmental area/substantia nigra co-cultivated with the striatum as well as the cellular expression of PDE2A and PDE10. The quantification shows a significant increase of fiber density in the border region induced by PDE2-Is (BAY60-7550; ND7001), comparable with the potential of the nerve growth factor and in contrast to PDE10-I (MP-10). Analysis of tyrosine hydroxylase-positive fibers indicated a significant increase after treatment with BAY60-7550 and nerve growth factor in relation to dimethyl sulfoxide. Additionally, a dose-dependent increase of intracellular cGMP levels in response to the applied PDE2-Is in PDE2-transfected HEK293 cells was found. In summary, our findings show that PDE2-Is are able to significantly promote axonal outgrowth in organotypic slice co-cultures, which are a suitable model to assess growth-related effects in neuro(re)generation.
- Subjects :
- Phosphodiesterase Inhibitors
Dopaminergic system
Biocytin
Organotypic slice co-culture
Substantia nigra
Striatum
Development
Biology
lcsh:RC346-429
Axonal outgrowth
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Organ Culture Techniques
Tracing
Developmental Neuroscience
medicine
Animals
Regeneration
Phosphodiesterase
Rats, Wistar
lcsh:Neurology. Diseases of the nervous system
Neurons
Tyrosine hydroxylase
Ventral Tegmental Area
lcsh:QP351-495
Axons
Rats
Cell biology
Substantia Nigra
Ventral tegmental area
lcsh:Neurophysiology and neuropsychology
Nerve growth factor
medicine.anatomical_structure
Neurology
chemistry
Phosphodiesterase 2
Neuroscience
Repair
Subjects
Details
- ISSN :
- 14248638 and 1424862X
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Neurosignals
- Accession number :
- edsair.doi.dedup.....a036cb20c2ad327c914a9887fb407a60