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Cerebral Cortex, Vol. 11, No. 4, 343-349, April 2001
© 2001 Oxford University Press

Caffeine-induced Telencephalic Vesicle Evagination in Early Post-implantation Mouse Embryos Involves cAMP-dependent Protein Kinase (PKA) Inhibition

Nadia Sahir, Christophe Mas, Francine Bourgeois, Michel Simonneau, Philippe Evrard and Pierre Gressens

INSERM E 9935, Hôpital Robert-Debré, Paris, France

Other studies have shown that caffeine accelerates telencephalic vesicle evagination in early post-implantation mouse embryos. The present study examines the effect of caffeine on gene modulation in post-implantation mouse embryos. Using mRNA differential display, we observed that caffeine increased gene expression of the regulatory subunit (RI{alpha}) of cAMP-dependent protein kinase (PKA). RT–PCR analysis confirmed an increase in expression of this gene in caffeine-exposed embryos when compared with saline-treated controls. Using a fluorescent substrate of PKA, we found that PKA activity in the presence of cAMP was lower in caffeine-treated embryos than in controls. Treatment with H89 and PKI(12-24)amide, two inhibitors of PKA activity, mimicked the effects of caffeine on telencephalic vesicle formation. Together these data suggest that in early post-implantation mouse embryos caffeine modulates gene expression of the RI{alpha} subunit of PKA and that caffeine-induced inhibition of PKA activity plays a role in early telencephalic evagination.


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