Wadzanai Masvosva, Marko Lehtonen, Mika Martiskainen, Jari Tiihonen, Pekka J. Karhunen, Kati Hanhineva, Jaana Rysä, Eloise Kok, Olli Kärkkäinen
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We identified 137 cases (24 females) with high cotinine levels, indicating nicotine exposure. For controls, we identified 82 subjects (20 females) with no cotinine in the frontal cortex or CSF samples and no known history of smoking based on medical records and autopsy reports. Cases had significantly higher levels of 1-methylhistamine (Cohen's <i>d</i> = 0.66, <i>p</i> < 0.0001) and N-acetylputrescine (<i>d</i> = 0.84, <i>p</i> < 0.0001), and lower levels of aspartic acid (<i>d</i> = −0.53, <i>p</i> < 0.001), 3-methylhistidine (<i>d</i> = −0.58, <i>p</i> = 0.0004) and taurine (<i>d</i> = −0.47, <i>p</i> = 0.0002) in the frontal cortex compared to controls. Compared to the frontal cortex, differences between cases and controls were smaller in the CSF samples. Most of the observed differences were similar in both sexes, with a few exceptions like low ergothioneine levels, observed especially in female cases. 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For controls, we identified 82 subjects (20 females) with no cotinine in the frontal cortex or CSF samples and no known history of smoking based on medical records and autopsy reports. Cases had significantly higher levels of 1-methylhistamine (Cohen's <i>d</i> = 0.66, <i>p</i> < 0.0001) and N-acetylputrescine (<i>d</i> = 0.84, <i>p</i> < 0.0001), and lower levels of aspartic acid (<i>d</i> = −0.53, <i>p</i> < 0.001), 3-methylhistidine (<i>d</i> = −0.58, <i>p</i> = 0.0004) and taurine (<i>d</i> = −0.47, <i>p</i> = 0.0002) in the frontal cortex compared to controls. Compared to the frontal cortex, differences between cases and controls were smaller in the CSF samples. Most of the observed differences were similar in both sexes, with a few exceptions like low ergothioneine levels, observed especially in female cases. 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引用次数: 0
摘要
吸烟是世界上可预防死亡的最重要的单一原因。吸烟会导致接触数千种化学物质,并扰乱生物途径。它影响几个器官,包括大脑,其作用是由烟碱乙酰胆碱受体介导的。女性似乎更容易受到吸烟对健康的负面影响。在这项研究中,我们关注的是人类死后额叶皮层和脑脊液(CSF)样本代谢谱的变化与高水平尼古丁代谢物可替宁的关系。我们使用非靶向代谢组学分析来自坦佩雷猝死研究队列的死后额叶皮层和脑脊液样本。我们确定了137例(24例女性)高可替宁水平,表明尼古丁暴露。作为对照,我们确定了82名受试者(20名女性),根据医疗记录和尸检报告,他们的额叶皮层或脑脊液样本中没有可替宁,也没有已知的吸烟史。与对照组相比,患者额叶皮层中1-甲基组胺(Cohen’s d = 0.66, p < 0.0001)和n -乙酰腐胺(d = 0.84, p < 0.0001)水平显著升高,天冬氨酸(d = - 0.53, p < 0.001)、3-甲基组氨酸(d = - 0.58, p = 0.0004)和牛磺酸(d = - 0.47, p = 0.0002)水平显著降低。与额叶皮层相比,脑脊液样本中病例和对照组之间的差异较小。大多数观察到的差异在两性中是相似的,只有少数例外,如麦角硫因水平低,特别是在女性病例中观察到。总之,吸烟或尼古丁暴露与代谢物的改变有关,这些代谢物与氧化应激和神经炎症的增加以及额叶皮层神经递质水平的降低有关。
Metabolic Alterations in Human Post-Mortem Frontal Cortex and Cerebrospinal Fluid Associated With High Levels of Nicotine Metabolite Cotinine
Cigarette smoking is the single most significant cause of preventable death in the world. Tobacco smoking causes exposure to thousands of chemicals and disrupts biological pathways. It impacts several organs, including the brain, where its effects are mediated by nicotinic acetylcholine receptors. Women seem to be more susceptible to the negative health effects of smoking. In this study, we focused on the changes in the metabolic profile of human postmortem frontal cortex and cerebrospinal fluid (CSF) samples associated with high levels of the nicotine metabolite cotinine. We used non-targeted metabolomics to analyse post-mortem frontal cortex and CSF samples from the Tampere Sudden Death Study cohort. We identified 137 cases (24 females) with high cotinine levels, indicating nicotine exposure. For controls, we identified 82 subjects (20 females) with no cotinine in the frontal cortex or CSF samples and no known history of smoking based on medical records and autopsy reports. Cases had significantly higher levels of 1-methylhistamine (Cohen's d = 0.66, p < 0.0001) and N-acetylputrescine (d = 0.84, p < 0.0001), and lower levels of aspartic acid (d = −0.53, p < 0.001), 3-methylhistidine (d = −0.58, p = 0.0004) and taurine (d = −0.47, p = 0.0002) in the frontal cortex compared to controls. Compared to the frontal cortex, differences between cases and controls were smaller in the CSF samples. Most of the observed differences were similar in both sexes, with a few exceptions like low ergothioneine levels, observed especially in female cases. In conclusion, smoking or nicotine exposure is associated with alterations in metabolites linked to increased oxidative stress and neuroinflammation, as well as reduced neurotransmitter levels in the frontal cortex.
期刊介绍:
Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields.
Addiction Biology includes peer-reviewed original research reports and reviews.
Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.