scholarly journals Correction: Activation of α-7 Nicotinic Acetylcholine Receptor Reduces Ischemic Stroke Injury through Reduction of Pro-Inflammatory Macrophages and Oxidative Stress

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0152218 ◽  
Author(s):  
Zhenying Han ◽  
Fanxia Shen ◽  
Yue He ◽  
Vincent Degos ◽  
Marine Camus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Inflammatory Macrophages ◽  
And Oxidative Stress

Abstract W P98: Activation of α7 Nicotinic Acetylcholine Receptor Reduces Pro-Inflammatory Macrophage and Improves Ischemic Stroke Recovery

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Zhenying Han ◽  
Fanxia Shen ◽  
Yue He ◽  
Vincent Degos ◽  
Marine Camus ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Stroke Recovery ◽  
Behavioral Tests ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Adhesive Removal ◽  
Inflammatory Macrophages

Background and Purpose: Inflammation influences stroke recovery. Activation of α7 nicotinic acetylcholine receptor (α7 nAchR) attenuates inflammation. We hypothesize that α7 nAchR agonist treatment reduces pro-inflammatory macrophages (M1) and improves ischemic stroke recovery. Methods: C57BL/6 mice underwent permanent distal middle cerebral artery occlusion (pMCAO). They were randomly assigned to 7 groups: injected intraperitoneally with 0.4 or 0.8 mg/Kg PHA568487 (PHA, α7 nAchR agonist), 4 or 6 mg/Kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline immediately after pMCAO, or with 0.8 mg/Kg PHA or 6 mg/kg MLA immediately and 24 hours after pMCAO. Behavior was assessed by corner and adhesive removal tests at 3, 7, and 14 days after pMCAO (n=12). Atrophic volume (n=7) and the percentage of total (CD68 + ) and M1 (CD11b + /Iba1 + ) macrophages (n=6) among total cells in the peri-infarct region were quantified 14 days after pMCAO. The expression of M1 (CD11b and iNOS) and M2 marker (CD206) were quantified using real-time RT-PCR (n=4). Results: Compared to the saline-treated mice, those treated with two doses of 0.8 mg/kg PHA performed better in both behavioral tests at 3 (adhesive: p=0.01, corner: p=0.02) and 7 (adhesive: p=0.005, corner: p=0.03) days, and in the adhesive removal test at 14 days (p=0.004) after pMCAO. They had smaller atrophic volume (16±7 mm 3 vs 26±5 mm 3 , p=0.008), and fewer total (9±2.5% vs 15.8±1.7%, p<0.001) and M1 (14±2.3% vs 20.6±4.2%, p=0.005) macrophages. Mice treated with two doses of 6 mg/kg MLA performed worse in the behavioral tests at all times (p<0.05), had larger atrophic volume (48±20 mm 3 , p=0.03), and more total (25±4.2%, p=0.0003) and M1 macrophages (28±4.5%, p=0.01). The expression of CD11b and iNOS decreased (p<0.05) in the PHA group, and increased (p=0.01) in the MLA group. CD206 expression increased (p=0.04) in the PHA group and did not change in the MLA group. One-dose treatment had no effect. Conclusions: Activation of α7 nAchR reduces pro-inflammatory macrophages in the peri-infarct region, which is associated with reduction of atrophic volume and improvement of behavioral recovery.

scholarly journals Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe-Qi Xu ◽  
Jing-Jing Zhang ◽  
Ni Kong ◽  
Guang-Yu Zhang ◽  
Ping Ke ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Autophagy Flux ◽  
Nicotinic Acetylcholine

The α7 nicotinic acetylcholine receptor (α7nAChR) belongs to the superfamily of cys loop cationic ligand-gated channels, which consists of homogeneous α7 subunits. Although our lab found that activation of α7nAChR could alleviate ischemic stroke, the mechanism is still unknown. Herein, we explored whether autophagy is involved in the neuroprotective effect mediated by α7nAChR in ischemic stroke. Transient middle cerebral artery occlusion (tMCAO) and oxygen and glucose deprivation (OGD/R) exposure were applied to in vivo and in vitro models of ischemic stroke, respectively. Neurological deficit score and infarct volume were used to evaluate outcomes of tMCAO in the in vivo study. Autophagy-related proteins were detected by Western blot, and autophagy flux was detected by using tandem fluorescent mRFP-GFP-LC3 lentivirus. At 24 h after tMCAO, α7nAChR knockout mice showed worse neurological function and larger infarct volume than wild-type mice. PNU282987, an α7nAChR agonist, protected against OGD/R-induced neuronal injury, enhanced autophagy, and promoted autophagy flux. However, the beneficial effects of PNU282987 were eliminated by 3-methyladenine (3-MA), an autophagy inhibitor. Moreover, we found that PNU282987 treatment could activate the AMPK-mTOR-p70S6K signaling pathway in the in vitro study, while the effect was attenuated by compound C, an AMPK inhibitor. Our results demonstrated that the beneficial effect on neuronal survival via activation of α7nAChR was associated with enhanced autophagy, and the AMPK-mTOR-p70S6K signaling pathway was involved in α7nAChR activation–mediated neuroprotection.

scholarly journals α7-Nicotinic Acetylcholine Receptor Agonist Ameliorates Nicotine Plus High-Fat Diet–Induced Hepatic Steatosis in Male Mice by Inhibiting Oxidative Stress and Stimulating AMPK Signaling

Endocrinology ◽  
2017 ◽  
Vol 159 (2) ◽  
pp. 931-944 ◽  
Author(s):  
Mohammad Kamrul Hasan ◽  
Theodore C Friedman ◽  
Carl Sims ◽  
Desean L Lee ◽  
Jorge Espinoza-Derout ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Steatosis ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
High Fat Diet ◽  
Male Mice ◽  
Hepatocyte Apoptosis ◽  
High Fat ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine

Abstract α7-Nicotinic acetylcholine receptor (α7nAChR) agonists confer protection against a wide variety of cytotoxic insults and suppress oxidative stress and apoptosis in various cell systems, including hepatocytes. We recently demonstrated that nicotine, when combined with a high-fat diet (HFD), triggers oxidative stress, activates hepatocyte apoptosis, and exacerbates HFD-induced hepatic steatosis in male mice. This study evaluates whether PNU-282987 (PNU), a specific α7nAChR agonist, is effective in preventing nicotine plus HFD–induced hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice-daily intraperitoneal injections of 0.75 mg/kg body weight (BW) of nicotine, PNU (0.26 mg/kg BW), PNU plus nicotine, or saline for 10 weeks. PNU treatment was effective in attenuating nicotine plus HFD–induced increase in hepatic triglyceride levels, hepatocyte apoptosis, and hepatic steatosis. The preventive effects of PNU on nicotine plus HFD–induced hepatic steatosis were mediated by suppression of oxidative stress and activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) together with inhibition of its downstream target sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-coenzyme A-carboxylase (ACC). We conclude that the α7nAChR agonist PNU protects against nicotine plus HFD–induced hepatic steatosis in obese mice. PNU appears to work at various steps of signaling pathways involving suppression of oxidative stress, activation of AMPK, and inhibition of SREBP1c, FAS, and ACC. α7nAChR agonists may be an effective therapeutic strategy for ameliorating fatty liver disease, especially in obese smokers.

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