Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A

• Published in: PloS one Vol. 4; no. 2; p. e4606
• Main Authors: Guedj, Fayçal, Sébrié, Catherine, Rivals, Isabelle, Ledru, Aurelie, Paly, Evelyne, Bizot, Jean C, Smith, Desmond, Rubin, Edward, Gillet, Brigitte, Arbones, Mariona, Delabar, Jean M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.02.2009; Public Library of Science (PLoS)
• Subjects: Alterations; analogs & derivatives; Analysis; Angiogenesis; Animals; antagonists & inhibitors; Antioxidants; Antioxidants - pharmacology; Apolipoproteins; Artificial chromosomes; Atherosclerosis; BASIC BIOLOGICAL SCIENCES; Biology; Brain; Brain - growth & development; Brain-derived neurotrophic factor; Catechin; Catechin - analogs & derivatives; Catechin - pharmacology; Cell cycle; Cell density; Consolidation; Defects; Developmental Biology/Neurodevelopment; diet; Dosage; Down syndrome; Down's syndrome; Dyrk Kinases; DYRK1A gene; Edema; Epigallocatechin gallate; Epigallocatechin-3-gallate; Flavonoids; Flavonoids - pharmacology; Gene Dosage; gene overexpression; Genes; Genetic engineering; genetically modified animals; genetics; Genomes; Gestation; Green tea; growth & development; hippocampus; Humans; Intellectual disabilities; Ischemia; Kinases; Learning; Magnetic resonance imaging; Memory; Mice; Mice, Transgenic; Morphogenesis; Morphology; mouse models; Neurological Disorders/Cognitive Neurology and Dementia; Neuronal Plasticity; neuroprotective effect; Neuroscience/Neuronal Signaling Mechanisms; pharmacology; Phenols; Phenols - pharmacology; physiology; Polyphenols; protein kinases; Protein Serine-Threonine Kinases; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - physiology; Protein-Tyrosine Kinases; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; Proteins; Rodents; Synaptic plasticity; Tea; Transgenic animals; Transgenic mice; visual object recognition; volume; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004606

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.