Background

Diesel particulate matter (DPM) constitutes a significant air pollutant that adversely affects neurological health through the olfactory pathway. Although extensive human epidemiological and animal research exists, the specific mechanisms underlying DPM-induced olfactory dysfunction have not been definitively elucidated.

Objective

This study aimed to conduct a comprehensive analysis of the behavioral, histological, and molecular changes in the olfactory bulb (OB) of mice following intranasal exposure to 10 mg/kg DPM for a duration of four weeks.

Results

Exposure to DPM led to notable olfactory impairment in the mice, characterized by an elevation in Iba-1-positive microglia, though without inducing neuronal cell death. Transcriptomic evaluation revealed 84 differentially expressed genes (DEGs) in the OB that met the criteria of fold change greater than 1.5 and a p value less than 0.05. Within this set, 55 genes were upregulated and 29 were downregulated. Gene ontology-based functional analysis revealed that these DEGs were primarily related to sensory organ morphogenesis, energy homeostasis, and the regulation of monocyte aggregation. Subsequent investigation using the Kyoto Encyclopedia of Genes and Genomes database identified enriched pathways connected to neuroactive ligand-receptor interactions and calcium signaling.

Conclusion

Our findings suggest a plausible association between DPM-induced olfactory dysfunction and disruptions in a range of molecular pathways. This hypothesis is supported by observed alterations in gene expression and the presence of mild neuroinflammation, primarily driven by microglial activation.

中文翻译：

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柴油颗粒物对小鼠嗅球的影响：来自行为、组织学和分子评估的见解

背景

柴油颗粒物 (DPM) 是一种重要的空气污染物，通过嗅觉途径对神经健康产生不利影响。尽管存在广泛的人类流行病学和动物研究，但 DPM 引起的嗅觉功能障碍的具体机制尚未明确阐明。

客观的

本研究旨在对鼻内暴露于 10 mg/kg DPM 持续 4 周后小鼠嗅球 (OB) 的行为、组织学和分子变化进行全面分析。

结果

暴露于 DPM 会导致小鼠明显的嗅觉障碍，其特征是 Iba-1 阳性小胶质细胞升高，但不会诱导神经元细胞死亡。转录组学评估显示 OB 中有 84 个差异表达基因 (DEG) 符合倍数变化大于 1.5 且p值小于 0.05 的标准。在这组基因中，55 个基因上调，29 个基因下调。基于基因本体的功能分析表明，这些差异表达基因主要与感觉器官形态发生、能量稳态和单核细胞聚集的调节有关。随后使用京都基因和基因组百科全书数据库进行的研究确定了与神经活性配体-受体相互作用和钙信号传导相关的丰富途径。

结论

我们的研究结果表明，DPM 引起的嗅觉功能障碍与一系列分子途径的破坏之间可能存在关联。这一假设得到了观察到的基因表达变化和主要由小胶质细胞激活驱动的轻度神经炎症的存在的支持。