Wadzanai Masvosva, Marko Lehtonen, Mika Martiskainen, Jari Tiihonen, Pekka J. Karhunen, Kati Hanhineva, Jaana Rysä, Eloise Kok, Olli Kärkkäinen
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引用次数: 0
Abstract
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.