Pence Halime Hanim, Kilic Ertugrul, Elibol Birsen, Kuras Sibel, Guzel Mustafa, Buyuk Yalcin, Pence Sadrettin
Department of Medical Biochemistry, Hamidiye School of Medicine, University of Health Sciences Türkiye, Istanbul, Turkey.
Department of Physiology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
Exp Brain Res. 2024 Dec 13;243(1):24. doi: 10.1007/s00221-024-06972-y.
Heroin addiction is one of the neuropsychiatric burdens that affects many genetic and epigenetic systems. While it is known that heroin may change the expressions of some genes in the brain during dependence, there is no detailed study related to which gene are mostly affected. Therefore, in the current study, we aimed to determine alterations in the miRNA profiles of rats' brains for providing a detailed analysis of molecular mechanisms in heroin addiction-related toxicology. Next generation global miRNA sequencing was used to predict potential miRNAs in prefrontal cortex (PC), hippocampus, ventral tegmental area (VTA), striatum, and Nucleus accumbens (NA) of rats that exposed to heroin by intravenous injections. The total daily dose was started with 2 mg/kg and ended with 10 mg/kg on the 10 day. In the striatum, miR-18a, miR-17-5p, miR-20a-5p, miR-106a, miR-301a-3p, miR872-5p, miR-15a-5p, miR-500-3p, and miR-339-5p expressions were upregulated by nearly 2-to-4 times with heroin. The expressions of hippocampal miR-153-3p, miR-130a-3p, miR-204-5p, miR-15b-5p, and miR-137-3p and the expressions of miR-872, miR-183-5p, miR-20a-5p, miR-325-5p, miR-379-5p, and miR-340-5p in the VTA were 2-times higher in the heroin-addicted rats. While there was nearly 2-times increase in the miR-129-1-3p and miR-3068-3p expressions in the NA, no change was noted in the PC due to heroin. The only heroin-dependent downregulation was observed in the expressions of striatal miR-450b-3p and miR-103-1-5p of VTA. These results suggested that heroin addiction might give harm to brain by altering cytokine balance and increasing neuroinflammation and apoptosis. In addition, neurons also try to compensate these abnormalities by enhancing neurogenesis and angiogenesis through several miRNAs in the different brain regions. In conclusion, the present study may provide a more integrated view of the molecular mechanism and a potential biomarker that will aid in clinical diagnosis and treatment of heroin-dependence.
海洛因成瘾是影响许多遗传和表观遗传系统的神经精神负担之一。虽然已知海洛因在成瘾过程中可能会改变大脑中某些基因的表达，但尚无关于哪些基因受影响最大的详细研究。因此，在本研究中，我们旨在确定大鼠大脑中miRNA谱的变化，以详细分析海洛因成瘾相关毒理学中的分子机制。采用下一代全局miRNA测序技术预测静脉注射海洛因的大鼠前额叶皮质（PC）、海马体、腹侧被盖区（VTA）、纹状体和伏隔核（NA）中的潜在miRNA。每日总剂量从2mg/kg开始，在第10天结束时达到10mg/kg。在纹状体中，miR-18a、miR-17-5p、miR-20a-5p、miR-106a、miR-301a-3p、miR872-5p、miR-15a-5p、miR-500-3p和miR-339-5p的表达因海洛因而上调了近2至4倍。海马体中miR-153-3p、miR-130a-3p、miR-204-5p、miR-15b-5p和miR-137-3p的表达以及VTA中miR-872、miR-183-5p、miR-20a-5p、miR-325-5p, miR-379-5p和miR-340-5p的表达在海洛因成瘾大鼠中高出2倍。虽然NA中miR-129-1-3p和miR-3068-3p的表达增加了近2倍，但PC中未因海洛因而出现变化。唯一因海洛因依赖而下调的是纹状体中miR-450b-3p和VTA中miR-103-1-5p的表达。这些结果表明，海洛因成瘾可能通过改变细胞因子平衡、增加神经炎症和细胞凋亡对大脑造成损害。此外，神经元还试图通过不同脑区中的几种miRNA增强神经发生和血管生成来补偿这些异常。总之，本研究可能为分子机制提供更全面的观点，并为海洛因依赖的临床诊断和治疗提供潜在的生物标志物。
