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 journalArticle

20 Citations (Scopus)

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

Fingerprint

Neurogenesis
Stem Cells
Anxiety
Nestin
Dendritic Spines
Neuronal Plasticity
Episodic Memory
Dentate Gyrus
Memory Disorders
Microglia
Caspase 3
Transgenic Mice
Cues
Dementia
Hippocampus
Cell Survival
Alzheimer Disease
Protein Isoforms
Cell Death
Cell Proliferation

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

Cite this

Pristerà, A., Saraulli, D., Farioli-Vecchioli, S., Strimpakos, G., Costanzi, M., di Certo, M. G., ... Canu, N. (2013). Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. Neurobiology of Aging, 34(11), 2551-2563. https://doi.org/10.1016/j.neurobiolaging.2013.05.010

Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. / Pristerà, Andrea; Saraulli, Daniele; Farioli-Vecchioli, Stefano; Strimpakos, Georgios; Costanzi, Marco; di Certo, Maria Grazia; Cannas, Sara; Ciotti, Maria Teresa; Tirone, Felice; Mattei, Elisabetta; Cestari, Vincenzo; Canu, Nadia.

In: Neurobiology of Aging, Vol. 34, No. 11, 11.2013, p. 2551-2563.

Research output: Contribution to journalArticle

Pristerà, A, Saraulli, D, Farioli-Vecchioli, S, Strimpakos, G, Costanzi, M, di Certo, MG, Cannas, S, Ciotti, MT, Tirone, F, Mattei, E, Cestari, V & Canu, N 2013, 'Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory', Neurobiology of Aging, vol. 34, no. 11, pp. 2551-2563. https://doi.org/10.1016/j.neurobiolaging.2013.05.010
Pristerà A, Saraulli D, Farioli-Vecchioli S, Strimpakos G, Costanzi M, di Certo MG et al. Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. Neurobiology of Aging. 2013 Nov;34(11):2551-2563. https://doi.org/10.1016/j.neurobiolaging.2013.05.010
Pristerà, Andrea ; Saraulli, Daniele ; Farioli-Vecchioli, Stefano ; Strimpakos, Georgios ; Costanzi, Marco ; di Certo, Maria Grazia ; Cannas, Sara ; Ciotti, Maria Teresa ; Tirone, Felice ; Mattei, Elisabetta ; Cestari, Vincenzo ; Canu, Nadia. / Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 11. pp. 2551-2563.
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