Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures.
Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures.
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睡眠障碍和可卡因滥用影响嘌呤和嘧啶核苷酸代谢特征。
DOI：
10.3390/metabo12090869
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发表时间：
2022-09-15
期刊：
影响因子：
4.1
通讯作者：
Samikkannu T
中科院分区：
文献类型：
--
作者：
Doke M;McLaughlin JP;Baniasadi H;Samikkannu T
昼夜节律紊乱会改变正常的睡眠-觉醒周期，从而增加药物滥用的可能性。药物滥用会破坏昼夜节律调节的多种稳态过程，并影响成瘾模式，包括对可卡因的渴望。昼夜节律与可卡因滥用之间的关系是复杂且双向的，破坏会影响大脑功能和代谢特征。因此，阐明昼夜节律变化和可卡因滥用对人类代谢组的影响可能为识别潜在生物标志物提供新的见解。我们在一项体内研究中研究了在有或没有昼夜节律睡眠中断 (CRSD) 的情况下服用可卡因对代谢水平的影响，并将其与健康对照进行比较。对对照、CRSD、可卡因和含可卡因的 CRSD 组进行代谢组学分析。使用液相色谱电化学阵列平台分析血浆代谢物浓度。与对照相比，我们鉴定出 242 种已知代谢物； CRSD加可卡因组中有26个、CRSD组有4个、可卡因组中有22个表达显着差异。有趣的是，在可卡因治疗组的 CRSD 中，与可卡因组相比，尿苷一磷酸 (p < 0.008)、腺苷 5'-二磷酸 (p < 0.044) 和肌苷 (p < 0.019) 的表达水平显着改变。总之，嘌呤和嘧啶代谢的改变提供了有关与长期接触可卡因和 CRSD 相关的能量分布和代谢途径变化的线索。
Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circadian rhythm and cocaine abuse is complex and bidirectional, and disruption impacts both brain function and metabolic profiles. Therefore, elucidating the impact of circadian rhythm changes and cocaine abuse on the human metabolome may provide new insights into identifying potential biomarkers. We examine the effect of cocaine administration with and without circadian rhythm sleep disruption (CRSD) on metabolite levels and compare these to healthy controls in an in vivo study. A metabolomics analysis is performed on the control, CRSD, cocaine, and CRSD with cocaine groups. Plasma metabolite concentrations are analyzed using a liquid chromatography electrochemical array platform. We identify 242 known metabolites compared to the control; 26 in the CRSD with cocaine group, 4 in the CRSD group, and 22 in the cocaine group are significantly differentially expressed. Intriguingly, in the CRSD with cocaine treatment group, the expression levels of uridine monophosphate (p < 0.008), adenosine 5′-diphosphate (p < 0.044), and inosine (p < 0.019) are significantly altered compared with those in the cocaine group. In summary, alterations in purine and pyrimidine metabolism provide clues regarding changes in the energy profile and metabolic pathways associated with chronic exposure to cocaine and CRSD.
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