Activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) reverses referred mechanical hyperalgesia induced by colonic inflammation in mice

2012 ◽  
Vol 63 (5) ◽  
pp. 798-805 ◽  
Author(s):  
Robson Costa ◽  
Emerson M. Motta ◽  
Marianne N. Manjavachi ◽  
Maíra Cola ◽  
João B. Calixto
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Mechanical Hyperalgesia ◽  
Colonic Inflammation ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Alpha 7

scholarly journals Alpha-7 nicotinic acetylcholine receptor agonists in intracerebral hemorrhage: an evaluation of the current evidence for a novel therapeutic agent

2013 ◽  
Vol 34 (5) ◽  
pp. E10 ◽  
Author(s):  
Eric S. Sussman ◽  
Christopher P. Kellner ◽  
Michael M. McDowell ◽  
Samuel S. Bruce ◽  
Simon G. Heuts ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Therapeutic Agent ◽  
Current Evidence ◽  
Secondary Injury ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Alpha 7 ◽  
Novel Therapeutic

Intracerebral hemorrhage (ICH) is the most deadly and least treatable subtype of stroke, and at the present time there are no evidence-based therapeutic interventions for patients with this disease. Secondary injury mechanisms are known to cause substantial rates of morbidity and mortality following ICH, and the inflammatory cascade is a major contributor to this post-ICH secondary injury. The alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists have a well-established antiinflammatory effect and have been shown to attenuate perihematomal edema volume and to improve functional outcome in experimental ICH. The authors evaluate the current evidence for the use of an α7-nAChR agonist as a novel therapeutic agent in patients with ICH.

scholarly journals The Association Between Alpha-7 Nicotinic Acetylcholine Receptor and Microglial Polarization in Spinal Cord Injury: Nicotine as an Alternative Therapy for Neuroinflammation

2020 ◽  
Author(s):  
Abolfazl Badripour ◽  
Kamyar Moradi ◽  
Zahra Ebrahim Soltani ◽  
Sayna Bagheri ◽  
Pasha Reza Shams Azar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Treated Group ◽  
Male Rats ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Cord Injury ◽  
Alpha 7

Abstract Background: Nicotine is an agonist of alpha-7 nicotinic acetylcholine receptor (α7 nAChR). The association between the expression of α7 nAChR and neuroinflammation has been extensively reported. Herein, we assessed the efficacy of Nicotine in the management of spinal cord injury (SCI) complications and mediating mechanisms.Methods: In this study, 64 male rats were randomly allocated to 7 SCI and a sham-operated groups. SCI was induced through an aneurysmal clip at the T9/T10 level. The group list consists of a non-treated group as the control, four Nicotine-treated groups receiving 0.5, 1, 1.5, and 3 mg/kg of the drug, a Methyllycaconitine (MLA, 1.5 mg/kg)-treated group, a group of rodents receiving MLA plus the most effective dosage of Nicotine, and a sham one. Locomotion and mechanical allodynia were assessed during 28 days using the Basso, Beattie, Bresnahan (BBB) and von Frey methods, respectively. In the end, spinal cord samples were taken to assess cavity formation, the expression levels of M1 and M2 macrophages, pro-inflammatory and anti-inflammatory factors, as well as α7 nAChR and NF-κB gene levels.Results: Repeated measures analysis revealed significant effect of time-treatment interaction on locomotion [F (42, 336) = 120.2, p < 0.001] and mechanical sensitivity [F (35, 280) = 45.47, p < 0.001]. Behavioral response to Nicotine was dose-dependent, and 1 mg/kg of this reagent was the most efficient dosage. H&E staining represented lesser histopathological disruptions in Nicotine-treated animals. SCI increased the M1/M2 ratio (p < 0.001) via shifting macrophages polarization towards M1 subset and 1 mg/kg of Nicotine could attenuate this ratio (p < 0.001) through reversing the shift. Meanwhile, Nicotine administration resulted in a significant elevation of α7 nAChR and a reduction of NF-κB genes. Finally, in the Nicotine group, there were declines in the levels pro-inflammatory biomarkers, including TNF-α, IL-1β, and IL-6, while IL-10 was found higher than the control group (p values < 0.05). MLA-treated groups showed almost none of the aforementioned alterations. Conclusion: Single-dose therapy with Nicotine could improve locomotor and sensory complications of SCI. Nicotine possible mechanism of action is through increasing the α7 nAChR level, which alleviates neuro-inflammation by changing microglial phenotyping.

scholarly journals Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms

2021 ◽  
Vol 12 ◽  
Author(s):  
María Recio-Barbero ◽  
Rafael Segarra ◽  
Arantzazu Zabala ◽  
Eduardo González-Fraile ◽  
Ana González-Pinto ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Negative Symptoms ◽  
Antipsychotic Treatment ◽  
Controlled Trials ◽  
Nicotinic Acetylcholine ◽  
Cognitive Domains ◽  
Receptor Agonists ◽  
Α7 Nachr ◽  
Alpha 7

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (α7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia.Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus α7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence.Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of α7 nAChR agonists for negative symptoms [standardized mean difference −0.28, 95% CI (−0.56 to −0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system.Conclusions: Current evidence is too weak to consider α7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.

Abstract P242: Nicotinic Acetylcholine Receptor Subunit α7 is Protective Against Angiotensin II-induced Aneurysm and Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Nayaab S Khan ◽  
Spyros Mavropoulos ◽  
Kaie Ojamaa
Keyword(s):  
Blood Pressure ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Low Dose ◽  
Histological Analysis ◽  
Inflammatory Activity ◽  
High Dose ◽  
Ang Ii ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr

Alpha7 nicotinic acetylcholine receptor (α7 nAChR), an integral component of the cholinergic nervous system is known to mediate cholinergic anti-inflammatory activity in various disease models such as sepsis, stroke and neurocognitive disorders. We report for the first time that the α7 nAChR -/- deficient mouse serves as a novel model of hypertension and aneurysm formation. Seven month old male WT and α7 nAChR -/- mice weighing 28-33g were infused with low dose Ang II (350 ng/kg/min) or high dose (700 ng/kg/min) or vehicle for 15 days using mini-osmotic pumps (Alzet, model 2004) implanted subcutaneously. Blood pressure (BP) was recorded on day 0,3,7,10 and 14. Mice were euthanized on day 15. Heart and body weights were measured, histological analysis was performed on the aortas and immune profile of peripheral blood was analyzed by flow cytometry. High dose Ang II resulted in 70% mortality from aneurysm rupture in α7 nAChR -/- mice starting as early as the 4 th day of infusion. While cardiac hypertrophy was not observed, low dose Ang II resulted in a sharp rise in blood pressure in α7 nAChR -/- beginning on the 3 rd day to 167±3.7 mmHg compared to 138±3.3 mmHg in WT treated mice. On day14 of low dose treatment, BP in α7 nAChR -/- rose to 171±4.2 vs.135±3.1 in WT mice. No changes were observed in BP of untreated WT or α7 nAChR -/- animals. Histological analysis revealed high grade aneurysm in aortas of α7 nAChR -/- mice treated with low dose Ang II, demonstrating a prominent germinal center within the false lumen and fibrous desmoplastic stroma. Increased infiltration of CD11B + monocytes, and myeloperoxidase + stained neutrophils were observed in these aortas but not in the aortas of similarly treated WT mice. Flow cytometric analysis showed 27% ± 3.9 CD11B + /CD45 + circulating monocytes and 48% ± 0.8 Ly6G + /CD45 + neutrophils in α7 nAChR -/- vs. 19% ± 3 monocytes and 11.85% ± 2.9 neutrophils in WT mice. No differences in the levels of circulating immune cells were observed in untreated mice of either genotype. These data support a protective role of α7 nAChR in hypertension and aneurysm, potentially acting through its cholinergic anti-inflammatory activity. The α7 nAChR -/- mouse may serve as a new genetic model of aneurysm relevant in studies of the human disease.

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.

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