Effect of TLR4/MyD88/NF- κB Signal Pathway on the Hippocampus of Methamphetamine-dependent CPP Rats

Yuan ZHANG; Tingna ZHU; Yuanyuan CAO; Pengliang LIU; Yihang WANG; Yamei WU; Lihua LI; Yongna ZHAO; Shijun HONG

doi:10.12259/j.issn.2095-610X.S20230225

Volume 44 Issue 2

Feb. 2023

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Article Navigation > Journal of Kunming Medical University > 2023 > 44(2): 7-13

Yuan ZHANG, Tingna ZHU, Yuanyuan CAO, Pengliang LIU, Yihang WANG, Yamei WU, Lihua LI, Yongna ZHAO, Shijun HONG. Effect of TLR4/MyD88/NF- κB Signal Pathway on the Hippocampus of Methamphetamine-dependent CPP Rats[J]. Journal of Kunming Medical University, 2023, 44(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20230225

Citation:

Yuan ZHANG, Tingna ZHU, Yuanyuan CAO, Pengliang LIU, Yihang WANG, Yamei WU, Lihua LI, Yongna ZHAO, Shijun HONG. Effect of TLR4/MyD88/NF- κB Signal Pathway on the Hippocampus of Methamphetamine-dependent CPP Rats[J]. Journal of Kunming Medical University, 2023, 44(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20230225

Citation:

Yuan ZHANG, Tingna ZHU, Yuanyuan CAO, Pengliang LIU, Yihang WANG, Yamei WU, Lihua LI, Yongna ZHAO, Shijun HONG. Effect of TLR4/MyD88/NF- κB Signal Pathway on the Hippocampus of Methamphetamine-dependent CPP Rats[J]. Journal of Kunming Medical University, 2023, 44(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20230225

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Effect of TLR4/MyD88/NF- κB Signal Pathway on the Hippocampus of Methamphetamine-dependent CPP Rats

doi: 10.12259/j.issn.2095-610X.S20230225

1.
School of Pharmaceutical Sciences & Yunnan Key Laboratory of Pharmacology for Natural Products
2.
） School of Forensic Medicine
3.
School of International Education ，Kunming Medical University，Kunming Yunnan 650500，China

Received Date: 2022-12-06
Available Online: 2023-01-18
Publish Date: 2023-02-25

Abstract

Abstract

Objective To study the effect of TLR4/MyD88/NF- κB signal pathway on the hippocampus of methamphetamine （MA） dependent conditioned place preference （CPP） rats, and inhibition of Toll like receptor 4 （TLR4） by specific inhibitor TAK-242, thereby reducing MA induced hippocampal neuroinflammation. Methods We established a model of MA （10 mg/kg, ip, 14 d） dependent CPP in rats. Rats were randomly divided into 4 groups: normal saline group, MA group, TAK-242 group, and MA+TAK-242 group. TAK-242 group and MA+TAK-242 group were intraperitoneally injected with inhibitor TAK-242 （3 mg/kg）, and MA+TAK-242 group was intraperitoneally injected with MA （10 mg/kg） one hour later. Protein and mRNA expression of TLR4, MyD88, TRAF6, IκB- α, p-IκB- α, NF- κ B p65, p-NF-Κb p65 in hippocampus of MA dependent CPP rats were tested by Western Blot test and fluorescent quantitative PCR, respectively. Results Compared with normal saline group, the expression of protein and mRNA of TLR4, MyD88, TRAF6, NF- κBp65 in MA group increased （P < 0.001 or P < 0.01）.The protein of IκB- α and mRNA expression of lactamase decreased （P < 0.01）, the expression of p-IκB- α and p-NF- κBp65 increased （P < 0.01 or P < 0.05）. Compared with MA group, the protein and mRNA expression of TLR4, MyD88, TRAF6, NF- κBp65 in MA+TAK-242 group decreased （P < 0.001, P < 0.01 or P < 0.05） . The expression of IκB- α protein and mRNA was increased （P < 0.01）, the expression of p-IκB- α and p-NF- κBp65 decreased （P < 0.01 or P < 0.05）. Conclusions MA dependency can be achieved by activating TLR4/MyD88/NF- κ B signal pathway, which can induce neuroinflammation on the hippocampus of methamphetamine-dependent CPP rats. The use of specific TLR4 inhibitors can attenuate MA induced neuroinflammation.
- Methamphetamine dependence,
- Conditional place preference,
- Hippocampus,
- TLR4/MyD88/NF- κ B signal transduction pathway

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