Detection of methamphetamine neurotoxicity in forensic autopsy cases.

Methamphetamine (METH) is a powerful stimulant drug of abuse with potent addictive and neurotoxic properties. METH neurotoxicity is characterized by the long-term depletion of striatal monoamines. METH-induced release of dopamine generates reactive hydrogen species, which are proposed to play an important role in METH neurotoxicity. The tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) levels and glial reactions in the striata of METH abusers were examined using immunohistochemical technique. Decreases in TH immunoreactivity and DAT levels were evident in METH users. Although significant differences in VMAT2 levels were not common, the levels of VMAT2--a stable marker of striatal dopaminergic terminal integrity--were remarkably reduced in some METH users. Further, significant increases were observed in the number of microglia in the striatum although the activation of glial cells was not evident. In addition, the expression of 72-kDa heat shock proteins (HSP72) in the brains of METH abusers was assessed. HSP72 immunoreactivity was observed in the hippocampus and other areas. These findings may be indicative of hyperthermia due to METH-induced neurotoxicity although it is possible that HSPs are induced by other effects of METH. Immunohistochemical detection of dopaminergic terminal marker deficits, glial reactions, and HSP induction might provide useful information regarding the pathophysiology of chronic and/or lethal METH use in cases of METH-related deaths, where METH intoxication may not be toxicologically demonstrated.