Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory

Andrea Pristerà, Daniele Saraulli, Stefano Farioli-Vecchioli, Georgios Strimpakos, Marco Costanzi, Maria Grazia di Certo, Sara Cannas, Maria Teresa Ciotti, Felice Tirone, Elisabetta Mattei, Vincenzo Cestari, Nadia Canu

Research output: Contribution to journalArticlepeer-review

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 ofprogenitor 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.

Original languageEnglish
Pages (from-to)2551-2563
Number of pages13
JournalNeurobiology of Aging
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Adult hippocampal neurogenesis
  • Anxiety
  • Dentate gyrus
  • Episodic-like memory
  • Neuronal progenitor cell
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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