ABSTRACT
The mechanism of methamphetamine toxicity and addiction is the key research direction of forensic toxicology, and the development of omics technology provides a new platform for further study of this direction. METH toxic damage and addiction are reflected differently in genes, ribonucleic acid (RNA) transcription, protein and metabolism. This article summarizes the achievements and shortcomings of multi-omics technologies such as genome, transcriptome, metabolome and proteome in the study of METH damage and addiction, and discusses the strategies and advantages of multi-omics combined analysis in the study of METH toxic damage and addiction mechanism, in order to provide more useful reference information for forensic toxicology of METH.
Subject(s)
Metabolome , Metabolomics , Methamphetamine/toxicity , Proteome , ProteomicsABSTRACT
OBJECTIVE@#To investigate the activation characteristics of microglia (MG) in the rats striatum with MA-induced neurotoxicity.@*METHODS@#Male Wistar rats were divided randomly into control group (n=24) and experimental group (n=24). The rats of experimental group were injected intraperitoneally with MA (15 mg/kg x 8 injections, at 12 hours interval). The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed.@*RESULTS@#In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the "fork-type". In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling "bush-like" or "amoeba-like". The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7 (P<0.001).@*CONCLUSION@#The continuous MA stimulation of the CNS results in prominent MG activation.
Subject(s)
Animals , Male , Rats , Corpus Striatum/pathology , Immunohistochemistry , Methamphetamine/toxicity , Microglia/ultrastructure , Microscopy, Electron, Scanning , Random Allocation , Rats, Wistar , Staining and Labeling , Time FactorsABSTRACT
Os efeitos da administraçäo crônica do mazindol (5 e 10 mg/kg i.p. e 60 mg/kg s.c) sobre a evoluçäo ponderal e a atividade da tirosina hidroxilase cerebral foram determinados em ratos machos jovens e idosos. O potencial anorético da droga foi observado através da avaliaçäo comparativa do peso corporal dos animais. A atividade da tirosina hidroxilase no estriato foi utilizada como parâmetro indireto da possível neurotoxicidade do mazindol. Nos ratos jovens notou-se uma perda significativa de peso aos 15 dias de tratamento, com recuperaçäo ascendente deste ao longo do tempo. Nos ratos idosos houve também perda de peso significativa; no entanto, tal recuperaçäo näo foi observada. Näo foram detectadas alteraçöes significativas da atividade enzimática em relaçäo aos grupos controles para ambas as idades. Estes resultados säo analisados a partir de dados encontrados na literatura