Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.
Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) - a member of a natural polyphenols family, found in great amount in green tea leaves - is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice.
Guedj
Fayçal
F
Functional and Adaptive Biology, Université Paris Diderot-Paris7 and CNRS, Paris, France.
Sébrié
Catherine
C
Rivals
Isabelle
I
Ledru
Aurelie
A
Paly
Evelyne
E
Bizot
Jean C
JC
Smith
Desmond
D
Rubin
Edward
E
Gillet
Brigitte
B
Arbones
Mariona
M
Delabar
Jean M
JM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000254:growth & development; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D018628:Gene Dosage; D006801:Humans; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D013662:Tea; D000097603:Dyrk Kinases
D000975:Antioxidants; D002392:Catechin; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D013662:Tea; D000097603:Dyrk Kinases; C045651:epigallocatechin gallate