Partial Depletion of Peripheral M1 Macrophages Reverses Motor Deficits in MPTP-Treated Mouse by Suppressing Neuroinflammation and Dopaminergic Neurodegeneration

Yan, Aijuan; Zhang, Yu; Lin, Jingya; Song, Lu; Wang, Xijin; Liu, Zhenguo

doi:10.3389/fnagi.2018.00160

Cited by 34 publications

(27 citation statements)

References 44 publications

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“…to deplete peripheral macrophages. This macrophage depletion method had been proven to be reliable and widely used in many models [41,46]. We also proved that the macrophage depletion e ciency of the liposome (Supplemental Figure 3).…”

Section: Macrophages Depletion Alleviatedcolonic Myenteric Neurons Insupporting

confidence: 62%

“…To further determine the role of macrophages in neurons injury following system treatment of vincristine, we conducted a direct veri cation through in vivo macrophage depletion. We speci cally depleted macrophages of mice by the clodronate liposomes, this method had been proven to be reliable and widely used in stroke models [46] and Parkinson's disease [41]. Our results showed that continuous macrophage depletion signi cantly reduced colonic proin ammatory factors and mitigated colonic myenteric neurons injury.…”

Section: Discussionmentioning

confidence: 82%

“…Control liposomes (200 µL of the order preparation; FormuMax) and saline were used as a control. These two liposomes were intraperitoneally injected the day before the vincristine treatment was started, and then repeated every 3 days [40,41]. This strategy ensured persistent depletion of macrophages throughout the vincristine treatment period.…”

Section: Drug Administration and Treatmentmentioning

confidence: 99%

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Vincristine Leads to Colonic Myenteric Neurons Injury via Stimulating M1 Macrophages Polarization

Gao¹,

Tang²,

Zhang³

et al. 2020

Preprint

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BackgroundVincristine is widely used in treatment of various malignant tumors. The clinical application of vincristine is accompanied by peripheral neurotoxicity. The effect of vincristine on enteric neurons and the underlying mechanism are still unclear. MethodsC57BL6/J mice were systematically treated with vincristine for 10 days, and macrophages were depleted using clodronate liposomes. The colonic myenteric plexus neurons were extracted. Macrophages from different parts were extracted in an improved way.ResultsIn the current study, we demonstrated that system treatment of vincristine resulted in colonic myenteric neurons injury, proinflammatory factors increase and total gastrointestinal transport time increase. Vincristine promoted the M1-type macrophages polarization individually or in coordination with LPS and increased proinflammatory factors IL-1β, IL-6, TNF-α via increasing the phosphorylation of ERK1/2 and p38. In addition, these proinflammatory factors led to colonic myenteric neurons apoptosis targeting on SGK1-FOXO3 pathway. Importantly, macrophage depletion alleviated colonic myenteric neurons injury and the increase of proinflammatory factors caused by system treatment of vincristine.ConclusionsSystem treatment of vincristine led to colonic myenteric neurons injury via stimulating M1 macrophages polarization which was alleviated by depletion of macrophages.

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Section: Macrophages Depletion Alleviatedcolonic Myenteric Neurons Insupporting

confidence: 62%

Section: Discussionmentioning

confidence: 82%

Section: Drug Administration and Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Vincristine Leads to Colonic Myenteric Neurons Injury via Stimulating M1 Macrophages Polarization

Gao¹,

Tang²,

Zhang³

et al. 2020

Preprint

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“…Similarly, it has previously been revealed that TNF -α mRNA expression is significantly mitigated by melatonin treatment [ 27 ]. Yan et al [ 28 ] found that clodronate liposome treatment reduced the mRNA expression of inflammatory cytokines, such as TNF -α, IL -1β, and IL -6, in the striatum and SNpc. Research has also shown that treatment with pioglitazone attenuates the activation of microglia and astrocytes in the striatum and SNpc in MPTP-intoxicated mice [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation

et al. 2018

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Parkinson’s disease (PD), a common adult-onset neurodegenerative disorder with complex pathological mechanisms, is characterized by the degeneration of dopaminergic nigrostriatal neurons. The present study demonstrated that the herbal medicines Hepad 1 and 2 protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6 mice and SH-SY5Y cells. Hepad 1 and 2 remarkably alleviated the enhanced expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, macrophage-1, and phosphorylated iκB-α) and apoptotic signals (Bcl-2-associated X protein, caspase-3, and poly [ADP-ribose] polymerase-1). Additionally, Hepad reduced MPTP-induced oxidative damage by increasing the expression of anti-oxidant defense enzymes (superoxide dismutase and glutathione S-transferase) and downregulating the levels of nicotinamide adenine dinucleotide phosphate oxidase 4. This study also showed that the neuroprotective effects of Hepad include anti-inflammatory, anti-apoptotic, and anti-oxidative properties, in addition to activation of the protein kinase B, extracellular-signal-regulated kinase, and c-Jun N-terminal kinase signaling pathways. Furthermore, oral administration of Hepad 1 and 2 attenuated the death of tyrosine hydroxylase-positive substantia nigra neurons that was induced by 20 mg/kg MPTP. Therefore, our results suggest that Hepad 1 and 2 are useful for treating PD and other disorders associated with neuro-inflammatory, neuro-apoptotic, and neuro-oxidative damage.

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“…It is modulated by a number of mediators including cytokines, chemokines, prostaglandins and substance P (1). The central nervous system (CNS) was reported to respond to peripheral inflammatory stimuli by initiating a local inflammatory response, also known as neuroinflammation (2). There are numerous critical features in the development of neuroinflammation, including glial activation, the accumulation of pro-inflammatory cytokines and the expression of adhesion molecules (1,3,4).…”

Section: Introductionmentioning

confidence: 99%

Protective role of fentanyl in lipopolysaccharide‑induced neuroinflammation in BV‑2 cells

Wang

Ying-jie

2018

Exp Ther Med

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Neurosurgery always results in neuroinflammation, which may activate microglial cells. Previous studies have demonstrated that fentanyl could be used for the induction or maintenance of anesthesia prior to surgery. However, it is unknown if fentanyl attenuates neuroinflammation prophylactically. Cell viability in groups that were treated with different concentrations of fentanyl (0.01, 0.1, 1 or 5 µmol/l) was analyzed by an MTT assay. BV-2 microglial cells were treated with lipopolysaccharide (LPS) at a concentration of 1 µg/ml to mimic neuroinflammation . BV-2 cells were pretreated with 5 µmol/l fentanyl prior to stimulation by LPS. The protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in the culture medium were assessed by ELISA. The mRNA level of toll-like receptor (TLR)4 was evaluated by reverse transcription-quantitative polymerase chain reaction analysis. The protein levels of TLR4, glycogen synthase kinase (GSK)-3β and phosphorylated (p)-GSK-3β in BV-2 cells were assessed by western blot analysis. The MTT assay demonstrated that low concentrations of fentanyl (0.01, 0.1 or 1 µmol/l) did not affect the cell viability of BV-2 cells, while 5 µmol/l fentanyl significantly reduced BV-2 cell viability. The results of ELISA revealed that LPS significantly upregulated the release of TNF-α, IL-1β and IL-10, which were repressed by fentanyl pretreatment. Fentanyl pretreatment significantly reduced the LPS-induced elevation of TLR4 at mRNA and protein levels as well as p-GSK-3β protein levels in BV-2 cells. In conclusion, fentanyl pretreatment protects BV-2 cells from LPS-induced neuroinflammation by inhibiting TLR4 expression and GSK-3β activation. Neuroinflammation induced by surgery serves an important role in the development of postoperative cognitive dysfunction (POCD) and targeting the TLR4 and GSK-3β signaling pathway may provide a novel therapeutic approach for the treatment of POCD.

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Partial Depletion of Peripheral M1 Macrophages Reverses Motor Deficits in MPTP-Treated Mouse by Suppressing Neuroinflammation and Dopaminergic Neurodegeneration

Cited by 34 publications

References 44 publications

Vincristine Leads to Colonic Myenteric Neurons Injury via Stimulating M1 Macrophages Polarization

Vincristine Leads to Colonic Myenteric Neurons Injury via Stimulating M1 Macrophages Polarization

Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation

Protective role of fentanyl in lipopolysaccharide‑induced neuroinflammation in BV‑2 cells

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