title: Tau isoform with three microtubule binding domains is a marker of new axons generated from the subgranular zone in the hippocampal dentate gyrus: implications for Alzheimer's disease.
abstract: In the adult hippocampal dentate gyrus, newborn granule cells grow dendrites into the molecular layer and send axons into the CA3 region. Several molecular markers have been used to analyze production of these new neurons; however, no good markers for new axons have been described. Here we demonstrate that tau protein isoform with three microtubule binding domains (3R-Tau) is a marker of those axons following an antigen retrieval protocol. By using retrovirus-mediated GFP transduction, GFP can be detected in a period of 7-14 days after viral infection. We also provide a "proof of principle" demonstration of the power of that labeling showing modulation of 3R-Tau positive axons under physiological conditions (exercise and aging) as well as in a FTDP-17 neurodegenerative model and Alzheimer's disease models (mice overexpressing AβPPsw, ind or GSK3β). We conclude that 3R-Tau would be an efficient marker and a valuable tool to study new axons in adult neurogenesis as well as in neurodegenerative processes.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC/UAM, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Llorens-Martin
authors.forename: Cátia M
authors.initials: CM
authors.lastname: Teixeira
authors.forename: Almudena
authors.initials: A
authors.lastname: Fuster-Matanzo
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Jurado-Arjona
authors.forename: Víctor
authors.initials: V
authors.lastname: Borrell
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Félix
authors.initials: F
authors.lastname: Hernández
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D064032:Calbindin 2; D064026:Calbindins; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005822:Genetic Vectors / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D064032:Calbindin 2; D064026:Calbindins; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; D064030:S100 Calcium Binding Protein G; D016875:tau Proteins; D049452:Green Fluorescent Proteins; D038362:Glycogen Synthase Kinase 3