Shotgun proteomics analysis of protein responding to methamphetamine addiction in rat cerebellum

Abstract

Background : Methamphetamine (METH) is an addictive psychostimulant drug that induces damages several regions of the brain, including the cerebellum. METH can induce some proteins changes in synaptic neurotransmission and signal transduction underlying the mechanism of drug addiction in several brain regions such as the striatum, hippocampus and nucleus accumbens. Nevertheless, few studies have examined the effects of METH in the cerebellum.

Objective : The aim of the current study was to investigate changes in the synaptic neurotransmission and signal transduction protein expression in rat cerebellum following METH exposure using proteomics technique.

Methods : Male Sprague-Dawley rats were treated with an escalating dose-METH binge and saline in control group for 15 days. Three samples from each group were pooled and proteins were extracted from the cerebellar tissues.
The proteomics, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was then performed to identify the protein associated with the METHinduced drug addiction.

Results : In the cerebellar samples, it was found that nine proteins were altered and mapped to synaptic transmission and signal transduction. In METH group, seven proteins were identified, including excitatory amino acid transporter 1, synaptotagmin-7, shisa-6, thioredoxin-related transmembrane protein 4, serine/ threonine-protein kinase SIK1, plexin-B3, calbindin, were found upregulation while two down-regulated proteins including cAMP-specific 3',5'-cyclic phosphodiesterase 4D and neuronal acetylcholine receptor subunit alpha-10 were observed.

Conclusion : The alteration of synaptic transmission and signal transduction proteins was found in the cerebellum following METH exposure. The results of this study provide evidence to support disturbance of protein expression in cerebellum in METH addiction.