title: Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory.
abstract: Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26-230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3-independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair.
authors.affiliation: Institute of Cellular Biology and Neurobiology, National Research Council and Fondazione Santa Lucia, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pristerà
authors.forename: Daniele
authors.initials: D
authors.lastname: Saraulli
authors.forename: Stefano
authors.initials: S
authors.lastname: Farioli-Vecchioli
authors.forename: Georgios
authors.initials: G
authors.lastname: Strimpakos
authors.forename: Marco
authors.initials: M
authors.lastname: Costanzi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: di Certo
authors.forename: Sara
authors.initials: S
authors.lastname: Cannas
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Felice
authors.initials: F
authors.lastname: Tirone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mattei
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cestari
authors.forename: Nadia
authors.initials: N
authors.lastname: Canu
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D003623:Dark Adaptation / Q000235:genetics; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005822:Genetic Vectors / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D064231:Nestin; D016875:tau Proteins; D001616:beta-Galactosidase; D004318:Doxycycline
keywords: Adult hippocampal neurogenesis; Anxiety; Dentate gyrus; Episodic-like memory; Neuronal progenitor cell; tau