Vol 9: Long-Term Exposure of Mice to Nucleoside Analogues Disrupts Mitochondrial DNA Maintenance in Cortical Neurons.Report as inadecuate



 Vol 9: Long-Term Exposure of Mice to Nucleoside Analogues Disrupts Mitochondrial DNA Maintenance in Cortical Neurons.


Vol 9: Long-Term Exposure of Mice to Nucleoside Analogues Disrupts Mitochondrial DNA Maintenance in Cortical Neurons. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 9: Long-Term Exposure of Mice to Nucleoside Analogues Disrupts Mitochondrial DNA Maintenance in Cortical Neurons.
This article is from PLoS ONE, volume 9.AbstractNucleoside analogue reverse transcriptase inhibitor NRTI, an integral component of highly active antiretroviral therapy HAART, was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier BBB and the complex microenvironment of the central nervous system CNS. In this study, the Balb-c mice were administered 50 mg-kg stavudine D4T, 100 mg-kg zidovudine AZT, 50 mg-kg lamivudine 3TC or 50 mg-kg didanosine DDI per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA mtDNA levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver except for 3TC and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.



Author: Zhang, Yulin; Song, Fengli; Gao, Ziyun; Ding, Wei; Qiao, Luxin; Yang, Sufang; Chen, Xi; Jin, Ronghua; Chen, Dexi

Source: https://archive.org/







Related documents