Cyclophosphamide induces the loss of taste bud innervation in mice.

IF 2.8 4区 心理学 Q1 BEHAVIORAL SCIENCES Chemical Senses Pub Date : 2024-01-01 DOI:10.1093/chemse/bjae010
Ryan M Wood, Erin L Vasquez, Krystal A Goyins, Eduardo Gutierrez Kuri, Kevin Connelly, Saima Humayun, Lindsey J Macpherson
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Abstract

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.

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环磷酰胺诱导小鼠味蕾神经失调
许多常见的化疗药物都会破坏味觉,从而导致食欲不振、营养失衡和生活质量下降,尤其是在治疗结束后味觉减退的情况下。环磷酰胺(CYP)是一种烷基化化疗药物,它通过对成熟的味觉受体细胞(TRCs)和味觉祖细胞群产生细胞毒性作用来影响味觉敏感性,从而延缓 TRCs 的替代能力。机理研究主要集中在味觉细胞上,然而味觉信号的传递需要味觉受体细胞与支配它们的味觉神经纤维之间的交流。在此,我们评估了环磷酰胺对支配味蕾的外周味觉神经纤维的影响。通过对舌头组织进行组织学分析,我们发现环磷酰胺会在用药后 4 天内减少漏斗状味蕾和环状味蕾的神经支配。为了更好地了解神经支配过程的动态变化,我们使用双光子眼内成像技术观察了 CYP 治疗后 20 天内各个漏斗状味蕾内的外周味觉神经纤维。我们发现,味觉纤维从味蕾本体缩回,但仍保留在中央乳头核心内。这些数据表明,除了TRCs,味觉神经纤维也会受到CYP处理的影响。由于味觉神经元和味觉神经元之间的连接必须重新建立才能发挥正常功能,因此味觉纤维应继续被纳入未来的研究中,以了解导致化疗引起的持续性味觉丧失的机制。
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来源期刊
Chemical Senses
Chemical Senses 医学-行为科学
CiteScore
8.60
自引率
2.90%
发文量
25
审稿时长
1 months
期刊介绍: Chemical Senses publishes original research and review papers on all aspects of chemoreception in both humans and animals. An important part of the journal''s coverage is devoted to techniques and the development and application of new methods for investigating chemoreception and chemosensory structures.
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