α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

Shen, Hui; Meng, Yanyan; Liú, Dan; Qin, Zheng; Pan, Lei; Wang, Wei; Kang, Jian

doi:10.2147/nss.s296701

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…We did not observe any sex differences in CIH-induced recollective memory impairment. Consistent with prior studies showing CIH-induced impairments in recollective memory in male rodents [51][52][53], we also found that CIH impaired recollective memory in male rats. CIH also decreased recollective memory in females, and our study is the rst to examine these relationships.…”

Section: Discussionsupporting

confidence: 92%

“…The in ammatory, OS, and behavioral phenotypes of CIH in males are clearly de ned. CIH increases in ammation [6, 47, 48], increases OS [6, 49,50], impairs recollective memory [51][52][53], impairs spatial learning and memory [47,[54][55][56], and increases anxiety-like behavior [51,52,57,58]. Studies examining sex as a biological variable in CIH are scarce.…”

Section: Introductionmentioning

confidence: 99%

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Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea

Mabry,

Bradshaw,

Gardner

et al. 2024

Preprint

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Background Obstructive sleep apnea (OSA) affects 10–26% of adults in the United States with known sex differences in prevalence and severity. OSA is characterized by elevated inflammation, oxidative stress (OS), and cognitive dysfunction. However, there is a paucity of data regarding the role of sex in the OSA phenotype. Prior findings suggest women exhibit different OSA phenotypes than men, which could result in under-reported OSA prevalence in women. To examine the relationship between OSA and sex, we used chronic intermittent hypoxia (CIH) to model OSA in rats. We hypothesized that CIH would produce sex-dependent phenotypes of inflammation, OS, and cognitive dysfunction, and these sex differences would be dependent on mitochondrial oxidative stress (mtOS). Methods Adult male and female Sprague Dawley rats were exposed to CIH or normoxia for 14 days to examine the impact of sex on CIH-associated circulating inflammation (IL-1β, IL-4, IL-6, IL-10, TNF-α), circulating OS, and behavior (recollective and spatial memory; gross and fine motor function; anxiety-like behaviors; and compulsive behaviors). A subset of rats was implanted with osmotic minipumps containing either a mitochondria-targeting antioxidant (MitoTEMPOL) or saline vehicle 1 week prior to CIH initiation to examine how inhibiting mtOS would affect the CIH phenotype. Results Sex-specific differences in CIH-induced inflammation, OS, motor function, and compulsive behavior were observed. In female rats, CIH increased inflammation (plasma IL-6 and IL-6/IL-10 ratio) and impaired fine motor function. Conversely, CIH elevated circulating OS and compulsivity in males. These sex-dependent effects of CIH were blocked by inhibiting mtOS. Interestingly, CIH impaired recollective memory in both sexes but these effects were not mediated by mtOS. No effects of CIH were observed on spatial memory, gross motor function, or anxiety-like behavior, regardless of sex. Conclusions Our results indicate that the impact of CIH is dependent on sex, such as an inflammatory response and OS response in females and males, respectively, that are mediated by mtOS. Interestingly, there was no effect of sex or mtOS in CIH-induced impairment of recollective memory. These results indicate that mtOS is involved in the sex differences observed in CIH, but a different mechanism underlies CIH-induced memory impairments.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea

Mabry,

Bradshaw,

Gardner

et al. 2024

Preprint

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“…Previous studies have demonstrated that α7nAchR played an important role in vagal-mediated cholinergic anti-inflammatory pathways, α7nAchR activation was involved in the protective effect of EA stimulation in ALI/ARDS ( 19 , 37 ). We next investigated whether EA could alleviate LPS-induced ferroptosis in lung tissues by activating α7nAchR ( 38 ). The western blot results showed that EA could upregulate the protein expression of α7nAchR in the lung tissues of LPS-treated mice, while the EA-induced upregulation of the expression of α7nAchR protein was significantly inhibited by methyllycaconitine (MLA), a selective α7nAchR antagonist ( Figures 4A, B ).…”

Section: Resultsmentioning

confidence: 99%

Electroacupuncture Alleviates LPS-Induced ARDS Through α7 Nicotinic Acetylcholine Receptor-Mediated Inhibition of Ferroptosis

et al. 2022

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Acute respiratory distress syndrome (ARDS) is an uncontrollable, progressive pulmonary inflammatory disease, and as a common clinical critical disease, there is no effective treatment available. Electroacupuncture (EA) therapy is a type of traditional Chinese medicine physiotherapy that can alleviate the inflammatory response. However, the potential mechanism of EA in the treatment of ARDS is not yet clear. Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation. Recently, emerging evidence has shown that ferroptosis is closely related to the occurrence and development of ARDS caused by various pathological factors. Here, we further investigated whether EA-mediated inhibition of ferroptosis in lung tissue could attenuate lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms. In this study, mice were administered LPS intraperitoneally to establish a model of LPS-induced ARDS. We found that EA stimulation could not only reduce the exudation of inflammatory cells and proteins in the alveolar lumen but also significantly alleviate the pathological changes of lung tissue, inhibit the production of proinflammatory cytokines and improve the survival rate of mice. Concurrently, we also found that ferroptosis events occurred in the lung tissue of LPS-induced ARDS mice, manifested by elevated iron levels, ROS production and lipid peroxidation. Intriguingly, our results showed that EA stimulation at the Zusanli (ST36) acupoint activated α7 nicotinic acetylcholine receptor (α7nAchR) in lung tissue mainly through the sciatic nerve and cervical vagus nerve, thus exerting anti-ferroptosis and pulmonary protective effects. Additionally, these effects were eliminated by methyllycaconitine (MLA), a selective antagonist of α7nAchR. In vitro experiments, activation of α7nAchR protected alveolar epithelial cells from LPS-induced ferroptosis. Furthermore, our experiments showed that the pulmonary protective effects of EA stimulation were effectively reversed by erastin, a ferroptosis activator. Collectively, we demonstrated that EA stimulation could alleviate LPS-induced ARDS by activating α7nAchR to inhibit LPS-induced ferroptosis in alveolar epithelial cells. Targeting and regulating ferroptosis in alveolar epithelial cells may be a potential intervention approach for the treatment of LPS-induced ALI/ARDS in the future.

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“…Following an aseptic laparotomy, these authors found a decrease of BDNF protein expression in the hippocampus, which was reversed by α7 nAChR activation and promoted by their inhibition. Additionally, in a mice model of chronic hypoxia‐induced cognitive dysfunction, systemic activation of α7 nAChRs improved cognitive impairment and increased BDNF protein expression in the hippocampus (Shen et al, 2021). These findings suggest that α7 nAChR‐induced increase in BDNF may be linked to pro‐cognitive effects of α7 nAChR activation.…”

Section: α7 Nachr As a Pharmacotherapy Tool In Memory Deficits And Co...mentioning

confidence: 99%

α7 nicotinic acetylcholine receptor in memory processing

Pastor

Medina

2023

Eur J of Neuroscience

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Information storage in the brain involves different memory types and stages that are processed by several brain regions. Cholinergic pathways through acetylcholine receptors actively participate on memory modulation, and their disfunction is associated with cognitive decline in several neurological disorders. During the last decade, the role of α7 subtype of nicotinic acetylcholine receptors in different memory stages has been studied. However, the information about their role in memory processing is still scarce. In this review, we attempt to identify brain areas where α7 nicotinic receptors have an essential role in different memory types and stages. In addition, we discuss recent work implicating—or not—α7 nicotinic receptors as promising pharmacological targets for memory impairment associated with neurological disorders.

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α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

Cited by 14 publications

References 36 publications

Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea

Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea

Electroacupuncture Alleviates LPS-Induced ARDS Through α7 Nicotinic Acetylcholine Receptor-Mediated Inhibition of Ferroptosis

α7 nicotinic acetylcholine receptor in memory processing

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