Selective Peripheral Taste Dysfunction in APP/PS1 Mutant Transgenic Mice.
Selective Peripheral Taste Dysfunction in APP/PS1 Mutant Transgenic Mice.
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DOI：
10.3233/jad-200376
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Macpherson LJ
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文献类型：
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作者：
Wood RM;Garcia Z;Daniels N;Landon SM;Humayun S;Lee HG;Macpherson LJ
先前的研究表明，味觉障碍在阿尔茨海默病的早期就会发生。味觉的缺失主要是由于外周感觉机制，还是中央处理，还是两者的结合，这是有争议的。我们目前的研究目的是结合APP/PS1转基因小鼠的行为和组织学数据，确定APP/PS1转基因小鼠是否表现出无条件的味觉偏好和回避行为缺陷，以及味觉障碍是否源于外周味觉系统的缺陷和/或味觉信息的中央处理问题。将APP/PS1转基因突变小鼠作为阿尔茨海默病模型。我们采用了一种简单的Gustometer测试来评估APP/PS1小鼠的即刻口感味觉反应。我们使用免疫组织化学方法检查舌头、味觉神经节和脑组织，以确定行为缺陷的细胞学基础。APP/PS1小鼠的苦味敏感度有显著的选择性降低。这些小鼠的舌环乳突中也失去了表达Trpm5的味觉感受器细胞。虽然我们没有观察到初级味觉感觉神经元内神经元胞体的明显丢失，但支配味蕾的神经元外周轴突的退化可能在观察到的Trpm5表达的味觉感受器细胞的丢失中起作用。这一数据支持通过选择性丧失味觉感受器细胞在AD外周味觉功能障碍中的潜在作用。有必要进一步研究这种缺陷在AD中的作用机制和病理意义。
Previous studies indicate that taste dysfunction occurs early in the development of Alzheimer’s Disease. It is debatable whether the deficit in taste is due primarily to peripheral sensory mechanisms or to central processing, or a combination of the two. The aim of our current study is to combine behavior and histological data in APP/PS1 transgenic mice to determine whether APP/PS1 transgenic mice show deficits in unconditioned taste preference and avoidance behaviors and whether taste impairments are due to defects in the peripheral taste system and/or problems with central processing of taste information. The APP/PS1 transgenic mutant mice were used as a model of Alzheimer’s Disease. We employed a brief-access gustometer test to assess immediate orosensory taste responses of APP/PS1 mice. We used immunohistochemistry to examine tongue, gustatory ganglion, and brain tissues to determine a cytological basis for behavioral deficits. There is a significant, selective reduction of bitter taste sensitivity in APP/PS1 mice. These mice also have a loss of TRPM5-expressing taste receptor cells in the circumvallate papillae of the tongue. While we observed no overt loss of neuron cell bodies within the primary gustatory sensory neurons, degeneration of the neurons’ peripheral axons innervating the taste bud may play a role in the observed loss of TRPM5-expressing taste receptor cells. This data supports a potential role for peripheral taste dysfunction in AD through the selective loss of taste receptor cells. Further study is necessary to delineate the mechanisms and pathological significance of this deficit in AD.