Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine through Suppressing Endoplasmic Reticulum Stress and Inflammation

Yang, Lihua; Guo, Yinli; Huang, Mengbin; Wu, Xiaoli; Li, Xiang; Chen, Guobing; Li, Ye; Bai, Jie

doi:10.3389/fneur.2018.00049

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…9 ). Notably, ER stress and neuroinflammation interact in nervous system diseases [ 59 , 60 ]. It is well accepted that inflammation is activated by ER stress, and high expression of multiple proinflammatory factors is relevant to neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 contributes to ER stress and inflammation: implications for Parkinson’s disease

Liu

Bai

et al. 2022

J Neuroinflammation

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Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Its molecular mechanism is still unclear, and pharmacological treatments are unsatisfactory. Transient receptor potential vanilloid 4 (TRPV4) is a nonselective Ca2+ channel. It has recently emerged as a critical risk factor in the pathophysiology of neuronal injuries and cerebral diseases. Our previous study reported that TRPV4 contributed to endoplasmic reticulum (ER) stress in the MPP+-induced cell model of PD. In the present study, we detected the role and the mechanism of TRPV4 in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Methods Intracerebral injection of an adeno-associated virus (AAV) into the substantia nigra (SN) of mice was used to knockdown or upregulate the expression of TRPV4 and intraperitoneal injection of MPTP. Rotarod and pole tests were used to evaluate the locomotor ability of mice. We used immunohistochemistry, Nissl staining and Western blot to detect the alterations in the number of tyrosine hydroxylase (TH)-positive neurons, Nissl-positive neurons, the levels of ER stress-associated molecules and proinflammatory cytokines in the SN. Results The SN was transfected with AAV for 3 weeks and expressed the target protein with green fluorescence. Knockdown of TRPV4 via injection of a constructed AAV-TRPV4 shRNAi into the SN alleviated the movement deficits of PD mice. Upregulation of TRPV4 via injection of a constructed AAV-TRPV4 aggravated the above movement disorders. The expression of TRPV4 was upregulated in the SN of MPTP-treated mice. Injection of AAV-TRPV4 shRNAi into the SN rescued the number of TH-positive and Nissl-positive neurons in the SN decreased by MPTP, while injection of AAV-TRPV4 induced the opposite effect. Moreover, MPTP-decreased Sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and pro-cysteinyl aspartate specific proteinase-12 (procaspase-12), MPTP-increased Glucose-regulated protein 78 (GRP78), Glucose-regulated protein 94 (GRP94) and C/EBP homologous protein (CHOP) were inhibited by AAV-TRPV4 shRNAi infection, and enhanced by AAV-TRPV4. In the same way, MPTP-decreased procaspase-1, MPTP-increased Interleukin-18 (IL-18), Cyclooxgenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) were inhibited by AAV-TRPV4 shRNAi, or further exacerbated by AAV-TRPV4. Conclusions These results suggest that TRPV4 mediates ER stress and inflammation pathways, contributing to the loss of dopamine (DA) neurons in the SN and movement deficits in PD mice. Moreover, this study provides a new perspective on molecular targets and gene therapies for the treatment of PD in the future.

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Section: Discussionmentioning

confidence: 99%

TRPV4 contributes to ER stress and inflammation: implications for Parkinson’s disease

Liu

Bai

et al. 2022

J Neuroinflammation

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“…Mice were divided into four groups: saline, morphine (20 mg/kg), TG + saline, and TG + morphine ( n = 7 per group). All procedures and protocols were approved by the animal ethics council of Kunming University of Science and Technology and were in accordance with the National Institutes of Health Guide for the Care and Use of Animals ( 12 ). The lab procedures were also approved by the local Committee on Animal Use and Protection of Yunnan province (No.…”

Section: Animals and Methodsmentioning

confidence: 99%

Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

Huang

Yang

et al. 2018

Front. Neurol.

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Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.

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“…Recently a dimeric fusion protein, thioredoxin-1, has also been frequently suggested as a new therapy for the cognitive alterations that occur in individuals with METH abuse. It blocks IL-1 signaling in the hippocampus, thereby attenuating the loss of METH-associated cognitive decline [21,72] . METH not only acts on IL-1 and IL-6, but also increases the level of interleukin-2 (IL-2) and decreases the level of IL-10 in the striatum.…”

Section: It Has Also Been Reported In the Literature That The Neuroin...mentioning

confidence: 99%

The role of the interleukin family in neuroinflammation caused by substance dependence

Fan

2024

Preprint

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Drug abuse is a universal phenomenon that happens across the world. And the neurotoxicity caused by drug abuse in the central nervous system has been extensively studied during the last decade. More recently, the role of drugs causing neuroinflammation, which would subsequently affect dopaminergic neurotoxicity, has aroused wide attention. This paper aims to present a literature review of the studies on the role of the interleukin family in substance-dependent neuroinflammation. Currently, the most studied cytokines in the interleukin family in the drug field are IL-1 and IL-6. In addition, based on the previous literature on changes in interleukin in neuroinflammation induced by different drugs, this paper identifies neuroinflammation-related diseases caused by interleukin families, and summarizes recent advances in the dynamics, mechanisms, immunomodulatory and anti-inflammatory effects that are related to the pathogenesis of these diseases. In conclusion, this review elucidates substance-dependent neurotoxicity from the perspective of interleukin alterations.

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Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine through Suppressing Endoplasmic Reticulum Stress and Inflammation

Cited by 6 publications

References 48 publications

TRPV4 contributes to ER stress and inflammation: implications for Parkinson’s disease

TRPV4 contributes to ER stress and inflammation: implications for Parkinson’s disease

Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

The role of the interleukin family in neuroinflammation caused by substance dependence

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