Abstract
Methamphetamine (METH) is a psychostimulant abused around the world. Emerging evidence indicates that METH causes brain damage. However, there are very few reports on METH-induced demyelination. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays the roles in protecting neurons from various stresses. However, whether Trx-1 resists demyelination induced by METH has not been reported. In this study, we found that METH-induced thin myelin sheaths in spinal cord, whereas Trx-1 overexpression transgenic (TG) mice restored the myelin sheaths thickness. The expressions of myelin-associated glycoprotein, myelin basic protein, and cyclin-dependent kinase 5 were decreased by METH, whereas these alterations were blocked in Trx-1 TG mice. The expressions of procaspase-12 and procaspase-3 were decreased by METH, the expression of calpain1 was increased by METH, whereas the alterations were suppressed in Trx-1 TG mice. As same as, the expressions of the extracellular signal-regulated kinase, nuclear factor κB, tumor necrosis factor-alpha, and interleukin-1beta were induced by METH, which were suppressed in Trx-1 TG mice. These data suggest that Trx-1 may play a critical role in resisting the METH-mediated demyelination in spinal cord through regulating endoplasmic reticulum stress and inflammation pathways.
Highlights
Methamphetamine (METH) is widely abused in the world and leads to increasing positive mood and euphoria [1, 2]
Associative learning between contextual cues and the rewarding effects of abused substances can result in conditioned place preference paradigm (CPP), a behavior observed in rodents [15]
We investigated whether extracellular signal-regulated kinase (ERK) and p-ERK were induced by METH in spinal cord, as we expected, the activity of p-ERK was increased after METH treatment, Figure 4 | Overexpression of thioredoxin-1 (Trx-1) regulated the expressions of major myelin proteins by methamphetamine (METH) in spinal cord. (A) Trx-1 overexpression inhibited decrease of myelin-associated glycoprotein (MAG) induced by METH in spinal cord. (B) Trx-1 overexpression prevented decrease of myelin basic protein (MBP) induced by METH in spinal cord. (C) Trx-1 overexpression restored decrease of cyclin-dependent kinase 5 (CDK5) induced by METH in spinal cord
Summary
Methamphetamine (METH) is widely abused in the world and leads to increasing positive mood and euphoria [1, 2]. The brain is the primary focus of most studies discovering neural mechanisms on addictive drugs [3]. The inseparable part of the central nervous system (CNS), spinal cord results from multiple pathologies due to its function of connecting the brain with the body. Trx-1 Resists Spinal Cord Demyelination injury (SCI) induced by addictive drugs attracts less attention. It has been reported that opioid addiction affects myelination [4]. It is still unknown whether METH induces demyelination in spinal cord
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