Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice

BMC Neuroscience, Dec 2016

Background It is known that tooth loss is known to be a risk factor for Alzheimer’s disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer’s disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNF-related mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). Results At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. Conclusions These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does.

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Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice

Takeda et al. BMC Neurosci Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice Yosuke Takeda 0 Hiroshi Oue 0 Shinsuke Okada 0 Akira Kawano 0 Katsunori Koretake 0 Makoto Michikawa 1 Yasumasa Akagawa 0 Kazuhiro Tsuga 0 0 Department of Advanced Prosthodontics, Hiroshima University Graduate School of Biomedical and Health Sciences , Hiroshima , Japan 1 Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan Background: It is known that tooth loss is known to be a risk factor for Alzheimer's disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer's disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/ Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNFrelated mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). Results: At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. Conclusions: These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does. Molar loss; Powder diet; Memory deficit; Brain-derived neurotrophic factor - Maintenance of healthy dental conditions and mastication has been believed to play a crucial role not only in oral function, but also in systemic conditions and brain function [1–3]. Retrospective studies have reported the relationship between oral health and cognitive impairment [4–6]. Community-dwelling persons with tooth loss are more likely to have impaired cognitive test performance, with those older than 45 years being more significantly affected [5]. Another study reported that the possession of fewer teeth in adulthood was significantly associated with incident of dementia [6] or tooth loss has been suggested as a possible epidemiological risk factor for Alzheimer’s disease (AD) [7]. Additionally, animal studies suggested that impairment of oral condition, including tooth loss, could lead to memory impairment [8–10]. © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic family, is widely expressed in the central nervous system and plays an important role in the regulation of hippocampal learning and memory processes [11]. Also, BDNF is a key molecule involved in the structural and functional plasticity of the hippocampal synapse. In addition, decreased BDNF levels may result in decreased hippocampal neurogenesis; BDNF expression is decreased in patients with AD and Parkinson’s disease [12–14]. BDNF actions include activation of insulin receptor substrate-1 (IRS-1/2), Pl-3K, and protein kinase B (Akt). BDNF binds to tyrosine kinase B (TrkB), which is a high affinity receptor of BDNF and activates a signal transduction cascade [15]. BDNF and its tyrosine kinase receptor, TrkB, are expressed in hypothalamic nuclei associated with satiety and locomotor activity [26]. Some reports suggest that BDNF might be associated with molar loss or soft diet [16, 17]. TrkB was also reduced in association with molar loss [16, 17]. Molar loss is associated with a reduction in t (...truncated)


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Yosuke Takeda, Hiroshi Oue, Shinsuke Okada, Akira Kawano, Katsunori Koretake, Makoto Michikawa, Yasumasa Akagawa, Kazuhiro Tsuga. Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice, BMC Neuroscience, 2016, pp. 81, 17, DOI: 10.1186/s12868-016-0319-y