Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Neurosci Lett. 2019 Nov 1;712:134478. doi: 10.1016/j.neulet.2019.134478. Epub 2019 Sep 3.
Damage to the reward brain system is regarded as a key consequence of narcotic drug abuse, including methamphetamine (METH). The Prefrontal cortex (PFC) is one of the brain areas associated with mesocortical pathway, which plays principal roles in cognitive behavior and memory function. In spite of the potential role of PFC in METH abuse, little is known about METH-induced neurotoxicity in PFC region. In this study, we examined neurotoxicity-associated molecular pathways such as inflammation, apoptosis and autophagy in PFC under the influence of METH using quantitative real time PCR (qPCR). Besides, the protein levels of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) as markers of synaptic plasticity and gliosis were inspected, respectively. Then we performed stereological analysis in METH-treated rats. Based on our findings, qPCR analysis revealed impaired autophagy, increased apoptosis and inflammation along with histological alterations in PFC, augmented astrogliosis as well as a significant reduction in the level of BDNF. Collectively, our molecular and histological data imply that METH administration in PFC region provoked differential expression changes in neurotoxicity-associated signaling cascades namely inflammation, apoptosis and autophagy coupled with significant PFC atrophy.
损伤奖励大脑系统被认为是一个关键的后果，包括冰毒（冰毒）滥用。前额叶皮层（PFC）是与中脑通路相关的脑区之一，在认知行为和记忆功能中起主要作用。尽管 PFC 在冰毒滥用中的潜在作用，但对于 PFC 区域中冰毒诱导的神经毒性知之甚少。在这项研究中，我们使用定量实时 PCR（qPCR）研究了 PFC 中与神经毒性相关的分子途径，如炎症、细胞凋亡和自噬。此外，还检测了脑源性神经营养因子（BDNF）和神经胶质纤维酸性蛋白（GFAP）作为突触可塑性和神经胶质增生标志物的蛋白水平。然后，我们对冰毒处理的大鼠进行了立体学分析。根据我们的发现，qPCR 分析显示 PFC 中自噬受损、细胞凋亡和炎症增加，以及组织学改变、星形胶质细胞增生增加和 BDNF 水平显著降低。总之，我们的分子和组织学数据表明，冰毒在 PFC 区域的给药引起了与神经毒性相关的信号级联的差异表达变化，即炎症、细胞凋亡和自噬，并伴有 PFC 萎缩的显著增加。
