title: Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro.
abstract: Epigallo-catechin-3-gallate (EGCG), found in the leaves of Camellia sinensis (green tea), has antioxidant- and scavenger-functions and acts neuroprotectively. It has been publicized as anti-aging remedy but data on potential cellular mechanisms are scarce. Recent studies claimed that EGCG specifically promotes neural precursor cell proliferation in the dentate gyrus of C57Bl/6 mice, without changes at the level of immature and mature new neurons. We here analyzed the effects of EGCG on adult hippocampal neurogenesis in male Balb/C mice and saw a different pattern. Two weeks of treatment with EGCG (0, 0.625, 1.25, 2.5, 5 and 10mg/kg) showed a dose-response curve that peaked at 2.5mg/kg of EGCG with significantly increased cell survival without affecting cell proliferation but decreasing apoptotic cells. Also, EGCG increased the population of doublecortin-(DCX)-expressing cells that comprises the late intermediate progenitor cells (type-2b and -3) as well as immature neurons. After EGCG treatment, the young DCX-positive neurons showed more elaborated dendritic trees. EGCG also significantly increased net neurogenesis in the adult hippocampus and increased the hippocampal levels of phospho-Akt. Ex vivo, EGCG exerted a direct effect on survival and neuronal differentiation of adult hippocampal precursor cells, which was absent, when PI3K, a protein upstream of Akt, was blocked. Our results thus support a pro-survival and a pro-neurogenic role of EGCG. In the context of the conflicting published results, however, potential genetic modifiers must be assumed. These might help to explain the overall variability of study results with EGCG. Our data do indicate, however, that natural compounds such as EGCG can in principle modulate brain plasticity.
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Ortiz-López
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico; Program of Master in Biological Sciences of UNAM, México, D.F., Mexico.
authors.forename: B
authors.initials: B
authors.lastname: Márquez-Valadez
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Gómez-Sánchez
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico; Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV-Zacatenco), Avanzados del Instituto Politécnico Nacional 2508, 07360 México D.F., Mexico.
authors.forename: M D C
authors.initials: MD
authors.lastname: Silva-Lucero
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Torres-Pérez
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico.
authors.forename: R I
authors.initials: RI
authors.lastname: Téllez-Ballesteros
authors.affiliation: CRTD - Center for Regenerative Therapies Dresden, Fetscherstraße 105, 01307 Dresden, Germany; Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Jalan Dr. Mansur 5, Medan, Indonesia.
authors.forename: M
authors.initials: M
authors.lastname: Ichwan
authors.affiliation: Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV-Zacatenco), Avanzados del Instituto Politécnico Nacional 2508, 07360 México D.F., Mexico.
authors.forename: M A
authors.initials: MA
authors.lastname: Meraz-Ríos
authors.affiliation: CRTD - Center for Regenerative Therapies Dresden, Fetscherstraße 105, 01307 Dresden, Germany; DZNE, German Center for Neurodegenerative Diseases, Dresden, Arnoldstrasse 18b, 01307 Dresden, Germany. Electronic address: gerd.kempermann@dzne.de.
authors.forename: G
authors.initials: G
authors.lastname: Kempermann
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico. Electronic address: gbernabe@imp.edu.mx.
authors.forename: G B
authors.initials: GB
authors.lastname: Ramírez-Rodríguez
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013662:Tea / Q000737:chemistry
chemical_list: D002392:Catechin; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013662:Tea; C000714847:Dcx protein, mouse; C045651:epigallocatechin gallate
keywords: EGCG; PI3K-Akt; adult neurogenesis; hippocampus; nutrition; survival