Soft-diet feeding after weaning affects behavior in mice: Potential increase in vulnerability to mental disorders.
Mastication is one of the most important oral functions, and the period during which mastication is acquired overlaps with the term of rapid development and maturation of the neural systems. In particular, the acquisition period after weaning is related to the potential onset of mental disorders. However, the roles of mastication during this period for brain development remain largely unknown. Therefore, we used a series of standard behavioral analyses, assessment of hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF), TrkB, and Akt1 in the hippocampus and frontal cortex of mice to investigate the effects of post-weaning mastication on brain function. We fed 21-day-old C57BL6/J male mice either a hard or a soft diet for 4weeks and conducted a series of standard behavioral tests from 7weeks of age. Further, histological analysis with bromodeoxyuridine was performed to compare hippocampal cell proliferation at 7 and 14weeks of age. Real-time polymerase chain reaction was performed to compare BDNF, TrkB, and Akt1 expression in the hippocampus and frontal cortex of 14-week-old mice. Compared to mice fed a hard diet (HDM), soft-diet mice (SDM) showed behavioral impairments, including decreased home cage activity, increased open field test activity, and deficits in prepulse inhibition. These results were similar to those observed in mouse models of schizophrenia. However, no effects were observed on anxiety-like behaviors or memory/learning tests. Compared to HDM, SDM showed significantly decreased hippocampal cell proliferation and hippocampal BDNF and Akt1 gene expression at 14weeks of age. A soft diet after weaning may have resulted in histological and molecular changes in the hippocampus and influenced outcomes of behavioral tests related to mental disorders. Our findings suggest that soft-diet feeding after weaning may affect both physical and mental development of mice, and may increase vulnerability to mental disorders.
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
K
K
Nose-Ishibashi
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan. Electronic address: junwata2000@ybb.ne.jp.
J
J
Watahiki
Research Resource Center, RIKEN Brain Science Institute, Saitama, Japan.
K
K
Yamada
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
M
M
Maekawa
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
A
A
Watanabe
Department of Oral Pathology and Diagnosis, School of Dentistry, Showa University, Tokyo, Japan.
G
G
Yamamoto
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
A
A
Enomoto
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan.
Y
Y
Matsuba
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
T
T
Nampo
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
T
T
Taguchi
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
Y
Y
Ichikawa
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan.
T C
TC
Saido
Department of Oral Pathology and Diagnosis, School of Dentistry, Showa University, Tokyo, Japan.
K
K
Mishima
Neuroinformatics Japan Center, RIKEN Brain Science Institute, Saitama, Japan.
Y
Y
Yamaguchi
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
T
T
Yoshikawa
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
K
K
Maki
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D018891:Dentate Gyrus / Q000502:physiology; D004032:Diet; D008297:Male; D008409:Mastication / Q000502:physiology*; D001523:Mental Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology; D012307:Risk Factors; D014886:Weaning
behavioral analysis; brain-derived neurotrophic factor; mental disorder; neurogenesis; prepulse inhibition; soft-diet feeding