Toll-Like Receptor 4 Mediates Methamphetamine-Induced Neuroinflammation through Caspase-11 Signaling Pathway in Astrocytes

Du, Songlin; Qiao, Dongfang; Chen, Chuanxiang; Chen, Si; Liu, Chao; Lin, Zhoumeng; Wang, Huijun; Xie, Wei‐Bing

doi:10.3389/fnmol.2017.00409

Cited by 67 publications

(55 citation statements)

References 64 publications

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“…Mice in the control group received an equivalent amount of saline. We selected this exposure paradigm after referring to the concentrations of short‐term METH exposure in humans (Du et al, ). At 24 hr after the last injection, the mice were euthanized, and midbrain and striatum tissues of brain were dissected.…”

Section: Methodsmentioning

confidence: 99%

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

et al. 2020

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Introduction Methamphetamine (METH) is a psychostimulant drug with complicated neurotoxicity, and abuse of METH is very common. Studies have shown that METH exposure causes alpha‐synuclein (α‐syn) accumulation. However, the mechanism of α‐syn accumulation has not been determined. Methods In this study, we established cell and animal models of METH intoxication to evaluate how METH affects α‐syn expression. In addition, to explore METH‐induced neurotoxicity, we measured the level of Parkin and the phosphorylation levels of α‐syn, Polo‐like kinase 2 (PLK2), the proteasome activity marker CD3δ, and the apoptosis‐related proteins Caspase‐3 and PARP. Parkin is a key enzyme in the ubiquitin–proteasome system. In addition, the effect of Parkin on METH‐induced neurotoxicity was investigated by overexpressing it in vitro and in vivo. Results METH exposure increased polyubiquitin and α‐syn expression, as did MG132. Furthermore, the level of Parkin and the interaction between Parkin and α‐syn decreased after METH exposure. Importantly, the increases in α‐syn expression and neurotoxicity were relieved by Parkin overexpression. Conclusions By establishing stable cell lines and animal models that overexpress Parkin, we confirmed Parkin as an important factor in METH‐induced α‐syn degradation dysfunction in vitro and in vivo. Parkin may be a promising target for the treatment of METH‐induced neurotoxicity.

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Section: Methodsmentioning

confidence: 99%

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

et al. 2020

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“…Following habituation for 1 wk, animals received 8 injections (15 mg/kg, i.p., at 12-h intervals) of either saline vehicle or Meth (.99% purity; National Institutes for Food and Drug Control, Guangzhou, China). This exposure paradigm was based on previous studies conducted by our team and others and was chosen to mimic human Meth abuse (6,25,(54)(55)(56)(57); the measured concentrations of Meth in the blood and brain (;0.2 mg/ml in blood and ;0.4 mg/g in brain) of rats 2 h after the final injection were close to the range of reported blood concentrations in Meth abusers [0.6-5 mg/ml (4-30 mM)] (54,56). The animals were euthanized 24 h after the last injection.…”

Section: Animals and Tissue Collectionmentioning

confidence: 99%

Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway

Huang

Luo

et al. 2018

The FASEB Journal

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Methamphetamine (Meth) is a widely abused psychoactive drug that primarily damages the nervous system, notably causing dopaminergic neuronal apoptosis. CCAAT-enhancer binding protein (C/EBPβ) is a transcription factor and an important regulator of cell apoptosis and autophagy. Insulin-like growth factor binding protein (IGFBP5) is a proapoptotic factor that mediates Meth-induced neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic reticulum (ER) stress-inducible gene involved in autophagic cell death through the mammalian target of rapamycin (mTOR) signaling pathway. To test the hypothesis that C/EBPβ is involved in Meth-induced IGFBP5-mediated neuronal apoptosis and Trib3-mediated neuronal autophagy, we measured the protein expression of C/EBPβ after Meth exposure and evaluated the effects of silencing C/EBPβ, IGFBP5, or Trib3 on Meth-induced apoptosis and autophagy in neuronal cells and in the rat striatum after intrastriatal Meth injection. We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity.-Xu, X., Huang, E., Luo, B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q., Liu, C., Lin, Z., Xie, W.-B., Wang, H. Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ-related signaling pathway.

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“…Within the central nervous system (CNS), astrocytes, microglia and endothelial cells can sense disturbed neuronal activity following injury, disease or neurotoxic agents (Clark et al, ; Shaerzadeh, Streit, Heysieattalab, & Khoshbouei, ). Besides the increase in DA neurotransmission, in brain areas receiving dopaminergic inputs, Amph promotes astrocyte reactivity stimulating cytokine production (Kadota & Kadota, ; Vicente‐Rodriguez et al, ; Du et al, ; Shah, Silverstein, Singh, & Kumar, ). Furthermore, microglial activation has been proposed as a hallmark for Amph derivatives‐induced neurotoxicity (Thomas et al, ), while gene and protein analyses in microglial cells indicate increased cytokine production and nitrosative stress after Amph exposure (Tocharus, Chongthammakun, & Govitrapong, ; Wisor, Schmidt, & Clegern, ).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC), and cognitive alterations. Brain angiotensin II, through angiotensin type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterward, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells, and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.

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Toll-Like Receptor 4 Mediates Methamphetamine-Induced Neuroinflammation through Caspase-11 Signaling Pathway in Astrocytes

Cited by 67 publications

References 64 publications

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

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