Role of microRNA-132 and Mecp2 in methamphetamine dependence / 中国药理学通报

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Current Situation of Methamphetamine Abuse and Related Research Progress / 法医学杂志

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.

Effects of gastrodin against SH-SY5Y cell autophagy induced by methamphetamine and underlying mechanisms / 中国药理学通报

Aim To investigate the effects of gastrodin on SH-SY5Y cell autophagy induced by methamphet-amine (METH) and the underlying mechanisms. Methods SY5Y cells were treated by METH with the concentration of 0.5,1.0,1.5,2.0,2.5,3.0 mmol·L-1for 24 h. The morphological changes were ob-served by microscopy,the expression of LC3-Ⅱ,Bec-lin-1,Akt,p-Akt,mTOR and p-mTOR were detected by Western blot. Gastrodin was added to the medium 1 h before METH treatment. Results The SY 5 Y cells were morphologically featured by shrinkage and den-drite disruption after exposed to METH(0~3 mmol· L-1),and autophagic vacuoles occurred in cytoplasm. The expression of LC3-Ⅱ increased over METH dose. Confocal results showed that LC3-Ⅱsignificantly in-creased in METH group as compared with control, while decreased in METH+ Gastrodin group. The ex-pression levels of LC3-Ⅱand Beclin-1 significantly in-creased (P<0.01) in METH group, p-mTOR and p-Akt decreased, and mTOR and Akt showed no signifi-cant difference as compared with control. However, the gastrodin could decrease the expression of LC3-Ⅱand Beclin-1 and increase the expression of mTOR,p-mTOR,Akt and p-Akt as compared with METH-trea-ted groups. Conclusions METH can induce SY5Y cells autophagy. The protective effect of gastrodin a-gainst METH-induced autophag may be related to gast-rodin regulation mTOR and Akt signaling pathway.

Expression of Astrocyte,Neuron,and Proinflammatory Cytokines Derived from Frontal Cortex of Methamphetamine Dependent rats after Gastrodin Administration / 昆明医科大学学报

Objective To observe the curative mechanism and effect of neurotoxicity injury induced by methamphetamine (MA) and the neuroprotective effects of gastrodin interfered. Whether the expression of astrocyte and proinflammatory cytokines has contributed to the effects of gastrodin.Methods 48 healthy male SD rats were randomly divided into three groups: control group (Daily intraperitoneal injection of saline for 8 weeks),MA group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg saline for 4 weeks) and gastrodin group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg gastrodin for 4weeks) . The behavioral changes of rats were measured by conditioned place preference ( CPP) and sterotyped behavior ( SB) induced by methamphetamine. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) and NEUN in rat frontal cortex.The expression of IL－6 and TNF－α were detected by quantity RT－PCR and westrn bloting.Results Compa MA depndent 4 weeks group with control group, the scores of sterotyped behavior of MA depndent groups had signficantly increased (P＜0.01) . Comparing MA depndent 4 weeks group with MA depndent 4 weeks+gastrodin group, the scores of sterotyped behavior of MA dependent 4 weeks group had obviously decreaseed (P＜0.01) . Compared with the control group, the expression of GFAP of MA dependent 4 weeks group decreased and the expression of NEUN increased. Compared MA dependent 4 weeks group with control group, the expression of IL－ 6 and TNF－α increased (P＜0.01) . Compared MA dependent 4 weeks+gastrodian group with MA dependent 4 weeks group, the expression of TNF－α and IL－6 significantly reduced (P＜0.01) . Conclusion The neurological damage induced by methamphetamine might be related to the activation of astrocytes and the high expression of inflammatory cytokines including IL－6 and TNF－α. Gastrodin could abate the neurological injury of methamphetamine dependence via reducing the activation of astrocytes and decreasing the expression of IL－6 and TNF－α.

Progress of Functional Imaging in Brain Structure and Functional Changes in People with Amphetamine Addiction / 昆明医科大学学报

Amphetamines abuse is defined as a chronic recurrent encephalopathy, and it is a global public health problem which seriously threatens the health of human and the social stability. Long-term abuse and addiction of amphetamines leads to structural and functional changes of specific encephalic regions. Further researches on these encephalic regions, the network of brain and biological information may be helpful to understanding drug abuse mechanism and possible therapeutic measures. Recently, a series of functional imaging techniques, including magnetic resonance imaging (MRI), functional magnetic resonance imaging (f MRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and positron emission tomography (PET), were used to detect different brain structural changes of the volume and density of encephalic regions, functional changes of cerebral blood flow and brain cognition. The results showed functional imaging techniques play significant roles to detect different structural and functional changes of the brain. Based on these results, the researchers aim to clarify the mechanisms of drug abuse. That is the main focus of this review.

Forensic Analysis of 20 Dead Cases Related to Heroin Abuse / 法医学杂志

OBJECTIVES@#To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases.@*METHODS@#Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes.@*RESULTS@#The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage （13 cases, 65%）, concurrent diseases caused by heroin abuse （3 cases, 15%）, inspiratory asphyxia caused by taking heroin （2 cases, 10%）, and heroin withdrawal syndrome （2 cases, 10%）.@*CONCLUSIONS@#The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation.

Changes of adenylate cyclase on cerebral regions related to mophine dependence in rats / 法医学杂志

OBJECTIVE@#To observe the changes of adenylate cyclase(AC) on cerebral regions related to morphine dependence in rats and investigate the relationship between the enzymological changes and the mechanism of morphine dependence.@*METHODS@#The technique of enzyme-histochemistry was used to detect the variations of AC of special seven cerebral regions including frontalis cortex, lenticula, corpus amygdaloideun, substantia nigra, hippocampus, periaqueductal gray and locus coerleus in morphine dependent rats. The enzymological changes were observed by optical microscope. Changes of gray degree of these cerebral regions were also observed by using the image analysis system.@*RESULTS@#Compared with those in control group, the contents of AC in morphine dependent groups were increased.@*CONCLUSION@#The contents of AC are increase in those regions. The mechanism of morphine dependence close related to the increasing of AC. The correlation of the mechanism of morphine dependence and up-regulation of AC/cAMP-PKA system is discussed.

The development of research on enzymes related to morphine-dependent / 法医学杂志

The mechanism of morphine dependent is a complex Procedure. It involves in many complex mechanisms such as the ultra-structure of synapse of special brain areas, neurotransmitter, enzymology, and so on. These mechanisms have closely correlation. In this paper we reveiwed the development in enzymological mechanism of morphine dependent enzymes including protein kinase (PK), nitric oxide synthase (NOS), superoxide dismutase (SOD), adenylate cyclase (AC), Succinate dehydrogenase (SDH)and 3beta-Hydroxy steroid dehydrogenase (3beta-HSD).