The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats

Abstract

Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis.

Selenium positively affects the proteome of 3 × Tg‐AD mice cortex by altering the expression of various key proteins: unveiling the mechanistic role of selenium in AD prevention

“…Down‐regulation of spectrin can be considered as a marker for neurodegeneration (Huh, Glantz, Je, Morrow, & Kim, ), which was validated in our results of AD mice cortices. It has been found that degradation of spectrin is caused by cellular calpains activated by high influx of calcium (Zhu et al, ). It's up‐regulation upon treatment with selenate in this study might be due to overall control of calcium influx.…”

Methamphetamine: Effects on the brain, gut and immune system

“…Recently, liquid chromatography-mass spectrometry (LC-MS/MS) analysis of extracts from rat brains following METH exposure identified changes in 18 proteins (11 from the hippocampus and 7 in the olfactory bulb); 13 of which were upregulated and 5 were downregulated. The modified proteins were predominantly involved in cell death, inflammation, oxidation and apoptotic pathways (25). In addition, alterations of endothelial cell structure and function, with increased levels of ROS, are observed in METH-related BBB disruptions (26,27).…”

Molecular mechanisms of programmed cell death in methamphetamine-induced neuronal damage

“…This neuropsychiatric complication is most commonly associated with METH-induced neurotoxicity. Continual use of METH in animals and humans has been shown to cause neurodegeneration of dopaminergic and serotonergic cells in the striatum, cortex, and hippocampi ( Zhu et al, 2016 ; Golsorkhdan et al, 2020 ). There are several mechanisms by which METH causes neurotoxicity, including direct damage to terminals, oxidative stress, mitochondrial dysfunction, neuronal excitability, endoplasmic reticulum stress, and neuroinflammation, resulting in dopaminergic neuron death ( Yang et al, 2018 ; Kim et al, 2020 ).…”