title: Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss.
authors.affiliation: Department of Pediatric Dentistry, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Pediatric Dentistry, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Kurahashi
authors.affiliation: Department of Prosthodontics, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.affiliation: Department of Pediatric Dentistry, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iinuma
authors.affiliation: Department of Pediatric Dentistry, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Biochemistry, Fujita Memorial Nanakuri Institute, Fujita Health University, 1865 Hisai-isshiki-cho, Tsu, Mie 514-1296, Japan.
authors.forename: Kenmei
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Department of Biochemistry, Fujita Memorial Nanakuri Institute, Fujita Health University, 1865 Hisai-isshiki-cho, Tsu, Mie 514-1296, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Shimpo
authors.affiliation: Department of Biochemistry, Fujita Memorial Nanakuri Institute, Fujita Health University, 1865 Hisai-isshiki-cho, Tsu, Mie 514-1296, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sonoda
authors.affiliation: Department of Anatomy, School of Medicine University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyusyu 807-8555, Japan.
authors.forename: Kagaku
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Seijoh University Graduate School of Health Care Studies, 2-172 Fukinodai, Tokai, Aichi 476-8588, Japan. Electronic address: kubo@seijoh-u.ac.jp.
authors.forename: Kin-ya
authors.initials: KY
authors.lastname: Kubo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004777:Environment; D006624:Hippocampus / Q000166:cytology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D051379:Mice; D008963:Molar; D010641:Phenotype; D065852:Spatial Memory; D016388:Tooth Loss / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine
keywords: Enriched environment; Hippocampus; Learning ability; Neurogenesis; Tooth loss