Inflammation but not programmed cell death is activated in methamphetamine-dependent patients: Relevance to the brain...

Animal studies have shown that methamphetamine (MA) induces neurodegeneration through programmed cell death, however, the effects of MA on human brain and the extent of induced neural degeneration is not well understood. Given that the dose and duration of MA administration differ in animals and humans, we evaluated MA effects on active users considering brain damage mechanisms. Nineteen active MA-dependent patients and 18 healthy controls performed the color-word Stroop task, during fMRI and their blood samples were collected. Human enzyme-linked immunosorbent assays (ELISA) and quantitative PCR were applied to measure circulating proteins and miRNAs involved in various programmed cell death pathways (apoptosis, necroptosis, and autophagy), brain damage and neuroinflammation. Results showed the performance deficit in color-word Stroop task in MA abusers as well as higher activations of the right inferior and middle temporal gyri detected by fMRI. Structural MRI revealed increased white matter volume in MA-dependent patients in the superior and medial frontal gyri, and left/right middle temporal gyrus. Molecular analyses detected no significant differences in the plasma levels of the studied proteins and miRNAs of MA-dependent patients and controls except the higher levels of MBP, S100B, and TNFα in MA abusers. Results showed that MA induced physiological and structural changes accompanied by inflammation and release of damage-associated molecules in MA-dependent patients.