Analysis of methamphetamine-induced neurotoxicity in the striatum of autopsied brains

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We demonstrated that decreases in tyrosine hydroxylase immunoreactivity in the nucleus accumbens and dopamine transporter in the nucleus accumbens and putamen were induced in methamphetamine (METH) users, whereas a significant difference of vesicular monoamine transporter-2 (VMAT2) was not evident between METH and control groups. However, in the nucleus accumbens of two METH users, levels of VMAT2, a stable marker of striatal dopaminergic terminal integrity, were reduced remarkably. These findings might indicate that dopaminergic terminal degeneration is induced in the striatum of some METH abusers. On the other hand, we observed little caspase・3 activation, indicative of apoptosis, in the striatal neurons of METH abusers. Overall, the findings of dopaminergic terminal markers were similar to those in the previous human study. Therefore, it is suggested that immunohistochemical techniques could be used to examine dopaminergic terminal marker levels and could also give useful informatio … More n on chronic and/or lethal METH use in cases of METH-related death, where METH intoxication may not be toxicologically demonstrated.We found significant increases in human glucose transporter-5-positive cells in chronic METH users; however, no proliferation of MHC class II-positive cells was found. GFAP-positive astrocytes increased, but not significantly, and vimentin expression was rarely observed. This study demonstrated a lack of microgliosis and astrogliosis in the striatum of chronic methamphetamine users. However, our observation of moderate glial reactions in human abusers is indicative of chronic METH abuse and suggests previously unrecognized roles of glial cells in the pathophysiology of METH abuse. Therefore, it is suggested that the immunohistochemical detection of glial reactions, together with the detection of decreases in dopaminergic terminal marker levels, would give useful information on METH abuse in cases of METH-related death.Further studies on brain-derived neurotrophic factor immunoreactivity and mitochondrial DNA deletion in the striatum of METH users are in progress. Less