背景:本系统综述旨在通过对现有文献的全面电子搜索和对其发现的回顾,评估物质使用的神经精神效应与内质网应激和未折叠蛋白反应(UPR)的发生之间的关联。
方法:通过主要数据库对1950年至2023年7月之间发表的研究文章进行了全面的电子文献检索,比如Scopus,WebofScience,谷歌学者,PubMed,PsycINFO,EMBASE,Medline和Cochrane图书馆。
结果:共选择21篇研究文章进行综述,由16项动物研究组成,四项人体研究和一项死后人脑样本研究。选定的研究表明,酒精,甲基苯丙胺,可卡因,阿片类药物和kratom暴露导致神经精神效应:如学习和记忆功能下降,执行功能障碍,酒精,甲基苯丙胺,阿片类药物和kratom依赖。这些作用与ER应激和UPR的激活和持久性以及BiP和CHOP表达的升高有关,并且ER应激的方向正在朝着PERK-eIF2α-ATF4-CHOP途径和神经元凋亡和神经变性的方向发展。大脑的各个区域。此外,在人类中常规使用kratom也有助于p-JNK表达的升高,表明内质网应激对IRE1-ASK1-JNK-p-JNK途径的进展,该途径与kratom使用障碍有关。然而,用某些化合物或生物制剂治疗可以逆转内质网应激的激活。
结论:酒精对神经精神的影响,甲基苯丙胺,可卡因,阿片类药物和kratom的使用可能与持续的ER应激和UPR相关。
BACKGROUND: This systematic
review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR) through comprehensive electronic search of existing literature and
review of their findings.
METHODS: A comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library.
RESULTS: A total of 21 research articles were selected for
review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress.
CONCLUSIONS: The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.