Proteomic analysis of cell-cell signaling alteration in rat frontal cortex following methamphetamine exposure
Keywords:
Methamphetamine, Frontal cortex, cell-cell signaling, ProteomicsAbstract
Methamphetamine (METH) is an addictive psychostimulant with potent effects on the central nervous system (CNS). Prolonged use of METH can impair brain structures and functions, especially the frontal cortex, a key brain involved in behavioral and cognitive functions. Moreover, METH has been reported change a number of proteins in neurotransmitter systems as well as proteins related to synaptic functions. Therefore, the objective of this study was to use the proteomic approach to investigate the differential expression of proteins related to synaptic function, including cell-cell signaling, in frontal cortex after METH administration. 20 male Sprague-Dawley rats were divided into 2 groups of control and METH; the rats were treated with saline and escalating binge dose of METH (0.1 to 4 mg/kg of METH (3 times /day), for 14 days and binge dose, 6 mg/kg (4 times /day) at day 15), respectively. The proteins in rat frontal cortex were investigated by proteomics technique. The results showed that there were 1,312 differentially expressed proteins in the frontal cortex of control and METH rats. Fifty-eight proteins were grouped in cell-cell signaling proteins. Thirty-six proteins were down-regulated and twenty-two proteins were up-regulated following METH administration. Furthermore, METH-interacted cell signaling proteins were mostly involved in neurotransmitter systems, 10 proteins in glutamatergic system, including 5 proteins in GABAergic system and 6 proteins in acetylcholine system. The results suggested that METH administration affects changes of proteins related in cell-cell signaling of the brain. These effects may implicate in METH-induced neurotoxicity. Studying in the differentially expressed protein by proteomic approach provides potential proteins related to METH-induced neurotoxicity
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