Mahmoudiasl G R, Abbaszadeh H A, Rezaei-Tavirani M, Abdollahifar M A, Khoramgah M S, Niknazar S, Darabi S, Roozbahany N A
Bratisl Lek Listy. 2019;120(10):769-776. doi: 10.4149/BLL_2019_129.
Methamphetamine (Meth) is one of the most important central nervous system (CNS) stimulant abuse drugs that cause long-term or permanent damage to different regions of the brain, particularly hippocampus, by neuronal apoptosis and inflammation. In this study, we evaluated Nod-like Receptor Protein 3(NLRP3) and Nod-like Receptor Protein1 (NLRP1) Inflammasome Activation in the Hippocampal Region of postmortem Meth Chronic User.
Molecular and histological analyses were conducted on the brain of 14 non-addicted and 11 Meth users separately. The expression level of NLRP1, NLRP3 was measured using western blotting and immunohistochemistry (IHC) techniques. Histopathological assessment was performed with stereological Cell Counting of hippocampal cells stained with hematoxylin and eosin (H et E). Moreover, Tunel staining was carried out in order to detect any kind of DNA damage.
Based on our findings using western blotting and immunohistochemistry assay, overexpression of NLRP1 and NLRP3 proteins in the hippocampal region of Meth addicts was observed. The stereological analysis in the hippocampus of the human brain revealed increased neurodegeneration. Furthermore, the increased rate of apoptosis and cell death were significant and confirmed by Tunel assay in the hippocampus of Meth groups.
Chronic Meth abuse could result in increases of NLRP1 and NLRP3 and induction of inflammation and apoptosis in the hippocampus in Meth groups (Tab. 1, Fig. 9, Ref. 40).
甲基苯丙胺(冰毒)是最重要的中枢神经系统(CNS)刺激性滥用药物之一,可通过神经元凋亡和炎症对大脑的不同区域,尤其是海马体造成长期或永久性损伤。在本研究中,我们评估了死后冰毒长期使用者海马区中Nod样受体蛋白3(NLRP3)和Nod样受体蛋白1(NLRP1)炎性小体的激活情况。
分别对14名非成瘾者和11名冰毒使用者的大脑进行分子和组织学分析。采用蛋白质免疫印迹法和免疫组织化学(IHC)技术检测NLRP1、NLRP3的表达水平。通过苏木精和伊红(H&E)染色的海马细胞立体细胞计数进行组织病理学评估。此外,进行Tunel染色以检测任何类型的DNA损伤。
基于我们使用蛋白质免疫印迹法和免疫组织化学分析的结果,观察到冰毒成瘾者海马区中NLRP1和NLRP3蛋白的过表达。人脑海马体的立体分析显示神经退行性变增加。此外,甲基苯丙胺组海马体中凋亡率和细胞死亡率的增加具有显著性,并通过Tunel检测得到证实。
慢性冰毒滥用可能导致甲基苯丙胺组海马体中NLRP1和NLRP3增加,并诱导炎症和凋亡(表1,图9,参考文献40)。