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

Neurobiol Aging. 2013 Nov;34(11):2551-63. doi: 10.1016/j.neurobiolaging.2013.05.010. Epub 2013 Jun 12.


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.

Keywords: Adult hippocampal neurogenesis; Anxiety; Dentate gyrus; Episodic-like memory; Neuronal progenitor cell; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Adult Stem Cells / physiology
  • Animals
  • Anxiety / genetics*
  • Dark Adaptation / genetics
  • Dendrites / pathology
  • Dendrites / ultrastructure
  • Disease Models, Animal
  • Doxycycline / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Genetic Vectors / physiology
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Maze Learning / physiology
  • Memory Disorders / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Nestin / genetics
  • Neurogenesis / genetics*
  • Time Factors
  • beta-Galactosidase / metabolism
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • Nerve Tissue Proteins
  • Nestin
  • tau Proteins
  • beta-Galactosidase
  • Doxycycline