It is suggested that masticatory dysfunction affects the central nervous system; however, the underlying mechanism remains unknown. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are known to play important roles in memory and learning. In this study, we examined the effects of mastication on memory, the expression levels of BDNF and TrkB, and the number of neurons in the hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into the control group (N = 7) fed chow pellets and the experimental group (N = 7) fed a liquid diet, which reduces mastication during eating. At 14 weeks of age, we performed a passive avoidance test and found that memory and learning ability were impaired in the experimental group compared with the control group. After the behavioral experiment, brains were harvested and analyzed morphologically and biochemically. In the hippocampus of the experimental group, the expression levels of BDNF were significantly higher, whereas those of TrkB were lower than those of the control group. In the cerebral cortex, these levels remained unchanged between the two groups. The ratio of phospho-p44/42 ERK/pan ERK, a downstream molecule of BDNF/TrkB signaling, in the experimental group was significantly lower than that of the control group in the cortex and hippocampus. The number of pyramidal neurons in the hippocampus was lower in the experimental group than in the control group. These findings suggest that reduced mastication induced by a liquid diet in early childhood may impair memory and learning ability, accompanied by neuronal loss in the hippocampus.
Mouth breathing caused by nasal obstruction affects the normal growth and development of craniofacial structures, including changes in the orofacial muscles. Tongue muscles play an important role in patency of the pharyngeal airway, and changes in the breathing pattern may influence tongue function. The purpose of this study was to evaluate the effect of unilateral nasal obstruction during growth on contractile properties of the tongue-protruding muscles. Sixty 6-day-old male Wistar albino rats were divided randomly into control (n = 30) and experimental (n = 30) groups. Rats in the experimental group underwent a unilateral nasal obstruction after cauterization of the external nostril at the age of 8 days, and muscle contractile characteristics were measured at 5, 7, and 9 wk of age. The specific parameters measured were twitch force, contraction time, half-decay time, tetanic force, and fatigue index. Repeated-measures multivariate analysis of variance was used for intergroup and intragroup statistical comparisons. Twitch contraction force and half-decay time were significantly increased in the experimental group at all ages. Tetanic forces at 60 and 80 Hz were significantly higher in the experimental group at all ages. The fatigue index was decreased significantly in the experimental group at the age of 5 wk. These results suggest that early unilateral nasal obstruction may increase the contraction force of the tongue-protruding muscles and prolong the duration of muscle contraction, which may influence the shape and development of the craniofacial complex.
Background & Aims
CD44 variant 9 (CD44v9)-positive cancer stem-like cells strongly contribute to the development and recurrence of gastric cancer. However, the origin of CD44v9-positive cells is uncertain.
Methods
CD44v9, β-catenin, and epithelial splicing regulatory protein 1 signals were assessed by real-time reverse-transcription polymerase chain reaction, immunoblot analysis, or immunofluorescence microscopy. Capping actin protein of muscle Z-line α subunit 1 (CAPZA1) expression was assessed by immunoblot analysis or immunohistochemical analysis of Mongolian gerbils' gastric mucosa or human biopsy specimens. Levels of oxidative stress were assessed by measuring malondialdehyde and protein carbonylation. Histone H3 acetylation levels in the
CAPZA1
proximal promoter region were measured by using chromatin immunoprecipitation analysis with an antibody against the acetylated histone H3 in human gastric carcinoma cell line (AGS) cells.
Results
CD44v9 is expressed in CAPZA1-overexpressing cells in human gastric cancer tissues. CAPZA1 overexpression enhanced expression of β-catenin, which is a transcription factor for CD44, and epithelial splicing regulatory protein 1, which increases alternative splicing of CD44 to generate CD44v9. CAPZA1-overexpressing cells after cytotoxin-associated gene A accumulation showed CD44v9 expression by inducing nuclear accumulation of β-catenin, concomitant with the enhancement of expression of Sal-like protein 4 and Krüppel-like factor 5, which encode reprogramming factors. Oxidative stress increased the CAPZA1 expression in AGS cells through the enhancement of histone H3 acetylation of
CAPZA1
promoter. CAPZA1 expression was increased depending on oxidative stress in
H pylori
–infected gastric mucosa.
Conclusions
CD44v9 expression is evoked from CAPZA1-overexpressing cells after accumulation of cytotoxin-associated gene A. Our findings provide important insights into the mechanisms underlying the development of CD44v9-positive cells.
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