Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment

Arch Oral Biol. 2016 Jan:61:1-7. doi: 10.1016/j.archoralbio.2015.10.006. Epub 2015 Oct 9.


Background and objective: Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss.

Design: Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured.

Results: Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability.

Conclusion: These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss.

Keywords: Enriched environment; Hippocampus; Learning ability; Neurogenesis; Tooth loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / metabolism
  • Bromodeoxyuridine
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Environment*
  • Hippocampus / cytology*
  • Hippocampus / physiopathology*
  • Immunohistochemistry
  • Male
  • Maze Learning
  • Mice
  • Molar
  • Phenotype
  • Spatial Memory*
  • Tooth Loss / physiopathology*


  • Brain-Derived Neurotrophic Factor
  • Bromodeoxyuridine