title: Chronic Methamphetamine Increases Alpha-Synuclein Protein Levels in the Striatum and Hippocampus but not in the Cortex of Juvenile Mice.
abstract: Methamphetamine is the second most widely used illicit drug worldwide. More than 290 tons of methamphetamine was synthesized in the year 2005 alone, corresponding to approximately ~3 billion 100 mg doses of methamphetamine. Drug addicts abuse high concentrations of methamphetamine for months and even years. Current reports in the literature are consistent with the interpretation that methamphetamine-induced neuronal injury may render methamphetamine users more susceptible to neurodegenerative pathologies. Specifically, chronic exposure to psychostimulants is associated with increases in striatal alpha-synuclein expression, a synaptic protein implicated in the pathogenesis of neurodegenerative diseases. This raises the question whether methamphetamine exposure affects alpha-synuclein levels in the brain. In this short report, we examined alpha-synuclein protein and mRNA levels in the striatum, hippocampus and cortex of adolescent male mice following a neurotoxic regimen of methamphetamine (24mg/kg/daily/14days). We found that methamphetamine exposure resulted in a decrease in the monomeric form of alpha-synuclein (molecular species <19 kDa), while increasing higher molecular weight alpha-synuclein species (>19 kDa) in the striatum and hippocampus, but not in the cortex. Despite the elevation of high molecular weight alpha-synuclein species (>19 kDa), there was no change in the alpha-synuclein mRNA levels in the striatum, hippocampus and cortex of mice exposed to methamphetamine. The methamphetamine-induced increase in high molecular weight alpha-synuclein protein levels might be one of the causal mechanisms or one of the compensatory consequences of methamphetamine-mediated neurotoxicity.
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: B
authors.initials: B
authors.lastname: Butler
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gamble-George
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: P
authors.initials: P
authors.lastname: Prins
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: A
authors.initials: A
authors.lastname: North
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Clarke
authors.affiliation: Department of Neuroscience, University of Florida School of Medicine, Gainesville, Fl 32611, USA.
authors.forename: H
authors.initials: H
authors.lastname: Khoshbouei
keywords: Aging; Alpha-synuclein; Methamphetamine; Parkinson’s disease; Synaptic transmission