Methamphetamine differentially alters expression of the peroxiredoxin antioxidant family of proteins in dopaminergic regions of the brain.

Abstract

Abuse of the psychostimulant and dopamine (DA) agonist, methamphetamine (METH), leads to neurodegeneration of DAergic neurons in the striatum (STR) and prefrontal cortex (PFC). This study focuses on the mRNA expression of the antioxidant family of proteins, peroxiredoxins (PRXs) that eliminate toxic free radicals resulting from oxidative stress such as that caused by METH. PRXs represent a family of six isoforms (PRX1-6) that have intra- and extra-cellular peroxidase activity. To understand how METH alters expression of these proteins, C57Bl/6J mice were exposed to saline or an abuse dosing paradigm of METH (5 mg/kg; i.p.) daily for 10 days. Real-time PCR analysis of PRX1-6 mRNA expression was performed on micro-dissected STR and PFC. In the PFC, METH induced a significant increase in PRX4 expression, an extracellular isoform and putative biomarker. This provides insight into a possible protective mechanism underlying METH-induced neurodegeneration. In the STR, METH induced a significant increase in PRX5 and decrease in PRX2. PRX5 is localized to the mitochondria and upregulated during times of oxidative stress similar to microglial activation during METH-induced neurotoxicity. PRX2 is an anti-apoptotic factor concentrated in the cytosol of neurons. Therefore, PRXs may play a role in METH-induced neurotoxicity in DAergic pathways of the brain.