English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Background and Purpose   cAMP  and pharmacological inhibition of  PDE 4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury ( SCI ). Using our previously described  in vitro   SCI  model, we studied the mechanisms by which  cAMP  modulators promote neurite outgrowth and myelination using enantiomers of the  PDE 4‐specific inhibitor rolipram and other modulators of downstream signalling effectors.    Experimental Approach  Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the  PDE 4‐specific inhibitor rolipram,  E pac agonists and  PKA  antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by  qPCR .    Key Results  Inhibition of the high‐affinity rolipram‐binding state ( HARBS ), rather than the low‐affinity rolipram binding state ( LARBS )  PDE 4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase  or PDE 4.    Conclusions and Implications   PDE 4 inhibitors targeted at the  HARBS  conformer or  E pac agonists may provide promising novel targets for the treatment of  SCI . Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of  SCI . These findings need to be confirmed  in vivo .

british journal of pharmacology

E pac and the high affinity rolipram binding conformer of  PDE 4 modulate neurite outgrowth and myelination using an  in vitro  spinal cord injury model