Soft-diet Feeding Inhibits Adult Neurogenesis in Hippocampus of Mice

Abstract

Our previous study showed that mice fed on a soft diet after weaning had reduced levels of brain-derived neurotrophic factor (BDNF) protein in the hippocampus after 3 months of age compared with mice fed on a hard diet. BDNF is one of the most effective promoters of neurogenesis in the hippocampus, and enhancement of BDNF production has been shown to enhance neural precursor cell proliferation in the dentate gyrus. We hypothesized that soft-diet feeding during development would reduce the proliferation rate of precursor cells, resulting in lower production of new neurons in the hippocampus. Male C57BL/6 mice pups were fed either a solid (hard-diet group) or powdered (softdiet group) diet starting at weaning. Three and six months after birth, mice of each group received intraperitoneal injections of bromodeoxyuridine (BrdU, 50 mg/kg body weight), twice a day for 3 consecutive days. After survival time of 1 day, 1 week, or 4 weeks, the mice were anesthetized and perfused transcardially. Newborn cells in the dentate gyrus were examined by immunohistochemistry using anti-BrdU antibody. In addition, phenotypically neuronal cells among the newborn cells were detected by immunofluorescent double labeling for BrdU and mature neuron-specific nuclear protein (NeuN) using anti-BrdU and anti-NeuN antibodies. Total number of BrdU-positive cells in the dentate gyrus was fewer in the 6-month-old mice than in the 3-month-old mice at any survival time investigated, and fewer in the soft-diet group than in the hard-diet group at 3 and 6 months of age. Neither soft-diet feeding nor aging affected ratio of phenotypically neuronal cells among newborn cells. These results indicate that insufficient mastication activity during development as well as aging restrains hippocampal neurogenesis in adulthood.

The impact of mastication on cognition: Evidence for intervention and the role of adult hippocampal neurogenesis

“…Brain-derived neurotrophic factor (BDNF) is one of the many signaling molecules involved in regulating AHN [14,18]. Interestingly, it has been demonstrated in studies that soft-diet feeding in mice leads to altered expression of BDNF and its receptor, Tryosine receptor kinase B (TrkB), in the hippocampus and restrained AHN, which resulted in behavioral impairments [12,19]. Impairment of this process results in impaired memory function, and studies involving ablation of these neurons demonstrates this.…”

“…The loss of teeth has also been suggested to be related to the development of senile dementia and Alzheimer's disease [9], with both conditions featuring loss of memory function and disturbed learning, areas that AHN has been hypothesised to modulate [4]. Several studies have investigated whether masticatory impairment affects AHN in mice and rat models, such as through soft-diet feeding (not requiring mastication) [10] and removal of molars [11] with another study demonstrating that a soft-diet in mice after weaning resulted in impaired AHN in later life [12]. A review of the relationship between mastication and dementia surmised that a correlation does indeed exist [13].…”

Neurogenesis in Adult Hippocampus

“…After comparing the cell proliferation in DG of adult mice fed on hard and soft diet, Yamamoto et al (Yamamoto et al, 2009) found that sufficient mastication activity enhanced hippocampal neurogenesis since that the total number of BrdU-labeled cells was fewer in the soft-diet group than in the hard-diet group at 3 and 6 months of age.…”

Stimulatory Effect of Whole Coffee Fruit Concentrate Powder on Plasma Levels of Total and Exosomal Brain-Derived Neurotrophic Factor in Healthy Subjects: An Acute Within-Subject Clinical Study

“…This product of the NTRK gene is expressed in several types of cells and tissues with major expression in neural cells and cardiomyocytes [4]. BDNF exerts several effects in the central nervous system: it regulates the development and differentiation of new neurons [5][6][7] and promotes neuron survival [8][9][10]; it influences mood and depression [11][12][13]; it controls sleep [14] and modulates appetite [15,16]. In addition, alterations in BDNF have been identified in various chronic neurodegenerative diseases [17].…”