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  Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures

Heine, C., Sygnecka, K., Scherf, N., Berndt, A., Egerland, U., Hage, T., et al. (2013). Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures. Neurosignals, 21(3-4), 197-212. doi:10.1159/000338020.

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Heine, C., Author
Sygnecka, K., Author
Scherf, Nico1, Author              
Berndt, A., Author
Egerland, U., Author
Hage, T., Author
Franke, H., Author
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1External Organizations, ou_persistent22              

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Free keywords: Axonal outgrowth; Biocytin; Development; Dopaminergic system; Organotypic slice co-culture; Phosphodiesterase; Regeneration; Repair; Tracing; Tyrosine hydroxylase
 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.

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Language(s): eng - English
 Dates: 2011-11-032012-02-292012-08-312013-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1159/000338020
PMID: 22947663
 Degree: -

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Title: Neurosignals
Source Genre: Journal
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Publ. Info: Basel, Switzerland : Karger
Pages: - Volume / Issue: 21 (3-4) Sequence Number: - Start / End Page: 197 - 212 Identifier: ISSN: 1424-862X
CoNE: https://pure.mpg.de/cone/journals/resource/111006469463156