Osada Kazumi, Kujirai Riyuki, Hosono Akira, Tsuda Masato, Ohata Motoko, Ohta Tohru, Nishimori Katsuhiko
Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University, Fujisawa, Japan.
The Research Institute of Health Science, Health Sciences University of Hokkaido, Tobetsu, Japan.
Front Behav Neurosci. 2023 Feb 1;16:983421. doi: 10.3389/fnbeh.2022.983421. eCollection 2022.
The oxytocin receptor (OXTR) knockout mouse is a model of autism spectrum disorder, characterized by abnormalities in social and olfactory behaviors and learning. Previously, we demonstrated that OXTR plays a crucial role in regulating aversive olfactory behavior to butyric acid odor. In this study, we attempted to determine whether coffee aroma affects the abnormal olfactory behavior of OXTR-Venus knock-in heterozygous mice [heterozygous OXTR (±) mice] using a set of behavioral and molecular experiments. Four-week repeated exposures of heterozygous OXTR (±) mice to coffee odor, containing three kairomone alkylpyrazines, rescued the abnormal olfactory behaviors compared with non-exposed wild-type or heterozygous OXTR (±) mice. Increased mRNA expression in the olfactory bulb and amygdala coincided with the rescue of abnormal olfactory behaviors. In addition, despite containing the kairomone compounds, both the wild-type and heterozygous OXTR (±) mice exhibited a preference for the coffee odor and exhibited no stress-like increase in the corticotropin-releasing hormone, instead of a kairomone-associated avoidance response. The repeated exposures to the coffee odor did not change oxytocin and estrogen synthetase/receptors as a regulator of the gonadotropic hormone. These data suggest that the rescue of abnormal olfactory behaviors in heterozygous OXTR (±) mice is due to the coffee odor exposure-induced OXTR expression.
催产素受体（OXTR）基因敲除小鼠是自闭症谱系障碍的一种模型，其特征为社交、嗅觉行为及学习方面的异常。此前，我们证明了OXTR在调节对丁酸气味的厌恶嗅觉行为中起关键作用。在本研究中，我们试图通过一系列行为学和分子实验来确定咖啡香气是否会影响OXTR-Venus基因敲入杂合小鼠[杂合OXTR（±）小鼠]的异常嗅觉行为。与未接触咖啡气味的野生型或杂合OXTR（±）小鼠相比，将杂合OXTR（±）小鼠四周重复暴露于含有三种信息素烷基吡嗪的咖啡气味中，可挽救其异常嗅觉行为。嗅球和杏仁核中mRNA表达的增加与异常嗅觉行为的挽救相一致。此外，尽管咖啡气味中含有信息素化合物，但野生型和杂合OXTR（±）小鼠均表现出对咖啡气味的偏好，且促肾上腺皮质激素释放激素未出现类似应激的增加，而非信息素相关的回避反应。重复暴露于咖啡气味中并未改变作为促性腺激素调节剂的催产素和雌激素合成酶/受体。这些数据表明，杂合OXTR（±）小鼠异常嗅觉行为的挽救是由于咖啡气味暴露诱导的OXTR表达所致。
