Periodontopathic bacteria such as Porphyromonas gingivalis produce several metabolites, including lipopolysaccharide (LPS) and n-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice. To elucidate the mechanisms by which metabolites such as LPS and BA, resulting from Porphyromonas gingivalis activity, induce immunological and physiological abnormalities in mice. In the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n = 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 μg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as “(moving distance on day 14 or 21)/(moving distance on day 0)”. Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities. Group BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice. We showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.

中文翻译：

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连续向小鼠龈内注射脂多糖和丁酸诱导异常行为和细胞因子浓度的变化

牙龈卟啉单胞菌等牙周病细菌会产生多种代谢物，包括脂多糖 (LPS) 和正丁酸 (BA)。过去的工作表明，牙周感染可能会导致小鼠的认知障碍。阐明由牙龈卟啉单胞菌活性产生的代谢物（如 LPS 和 BA）诱导小鼠免疫和生理异常的机制。在目前的工作中，28 只雄性 ICR 小鼠被放置在开阔的场地中，并记录了它们覆盖的总距离 (cm/600 s)。根据移动距离，将小鼠分为 4 组（n = 7），连续 32 天向其牙龈组织注射以下物质：生理盐水（C）、5 mmol/L BA（B）、1 μg/小鼠LPS (L) 和 BA-LPS (BL) 溶液。在第 14 天和第 21 天还测量了小鼠覆盖的距离，他们的习惯得分被视为“（第 14 天或第 21 天的移动距离）/（第 0 天的移动距离）”。之后，解剖小鼠，分析海马基因表达以及血浆和大脑中短链脂肪酸、神经递质和细胞因子的浓度。此外，固定小鼠脑和肝组织并目视评估组织病理学异常。BL 组在第 14 天的适应评分明显高于 C 和 B。LPS 在第 21 天诱导更高的适应评分。LPS 诱导白细胞介素 (IL)-6 和脑源性神经营养因子的 mRNA 水平显着降低，增加神经营养性酪氨酸激酶受体 2 型。在血浆和大脑中，LPS 均诱导醋酸盐显着增加。此外，LPS 显着增加大脑中的乙酰胆碱。仅在血浆中，LPS 和 BA 显着降低单核细胞趋化蛋白 1 (MCP-1)。然而，虽然 LPS 显着降低了酪氨酸，但 BA 显着增加了酪氨酸。最后，LPS 显着降低血浆中的 IL-6 和肿瘤坏死因子。在小鼠的肝脏或脑组织中未检测到组织病理学异常。我们表明注射 LPS 和/或 BA 诱导小鼠似乎不知疲倦地移动，并且注射 LPS 和 BA 都强烈诱导血浆中 MCP-1 的减少。我们得出结论，LPS 和 BA 可能对诱导和/或加重小鼠的异常行为至关重要。LPS 显着降低血浆中的 IL-6 和肿瘤坏死因子。在小鼠的肝脏或脑组织中未检测到组织病理学异常。我们表明注射 LPS 和/或 BA 诱导小鼠似乎不知疲倦地移动，并且注射 LPS 和 BA 都强烈诱导血浆中 MCP-1 的减少。我们得出结论，LPS 和 BA 可能对诱导和/或加重小鼠的异常行为至关重要。LPS 显着降低血浆中的 IL-6 和肿瘤坏死因子。在小鼠的肝脏或脑组织中未检测到组织病理学异常。我们表明注射 LPS 和/或 BA 诱导小鼠似乎不知疲倦地移动，并且注射 LPS 和 BA 都强烈诱导血浆中 MCP-1 的减少。我们得出结论，LPS 和 BA 可能对诱导和/或加重小鼠的异常行为至关重要。