Fiche publication
Date publication
septembre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GUEANT Jean-Louis
Tous les auteurs :
Pourie G, Martin N, Bossenmeyer-Pourie C, Akchiche N, Gueant-Rodriguez RM, Geoffroy A, Jeannesson E, El Hajj Chehadeh S, Mimoun K, Brachet P, Koziel V, Alberto JM, Helle D, Debard R, Leininger B, Daval JL, Gueant JL
Lien Pubmed
Résumé
Deficiency in the methyl donors vitamin B12 and folate during pregnancy and postnatal life impairs proper brain development. We studied the consequences of this combined deficiency on cerebellum plasticity in offspring from rat mothers subjected to deficient diet during gestation and lactation and in rat neuroprogenitor cells expressing cerebellum markers. The major proteomic change in cerebellum of 21-d-old deprived females was a 2.2-fold lower expression of synapsins, which was confirmed in neuroprogenitors cultivated in the deficient condition. A pathway analysis suggested that these proteomic changes were related to estrogen receptor alpha (ER-alpha)/Src tyrosine kinase. The influence of impaired ER-alpha pathway was confirmed by abnormal negative geotaxis test at d 19-20 and decreased phsophorylation of synapsins in deprived females treated by ER-alpha antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP). This effect was consistent with 2-fold decreased expression and methylation of ER-alpha and subsequent decreased ER-alpha/PPAR-gamma coactivator 1 alpha (PGC-1alpha) interaction in deficiency condition. The impaired ER-alpha pathway led to decreased expression of synapsins through 2-fold decreased EGR-1/Zif-268 transcription factor and to 1.7-fold reduced Src-dependent phosphorylation of synapsins. The treatment of neuroprogenitors with either MPP or PP1 (4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-N-(4-phenoxyphenyl)-4-quinazolinamine, SKI-1, Src-l1) Src inhibitor produced similar effects. In conclusion, the deficiency during pregnancy and lactation impairs the expression of synapsins through a deregulation of ER-alpha pathway.
Référence
FASEB J. 2015 Sep;29(9):3713-25
