α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia
Hui Shen, Yanling Meng, Dan Liu, Zheng Qin, Hong Huang, Lei Pan, Wei Wang, Jian Kang Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Wei WangInstitute of Respiratory Disease, The First Hospital of China M...
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Dove Medical Press
2021
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oai:doaj.org-article:5c0d2f10ea344dc49bbc6092469d26a32021-12-02T14:36:01Zα7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia1179-1608https://doaj.org/article/5c0d2f10ea344dc49bbc6092469d26a32021-05-01T00:00:00Zhttps://www.dovepress.com/alpha7-nicotinic-acetylcholine-receptor-agonist-pnu-282987-ameliorates-peer-reviewed-fulltext-article-NSShttps://doaj.org/toc/1179-1608Hui Shen, Yanling Meng, Dan Liu, Zheng Qin, Hong Huang, Lei Pan, Wei Wang, Jian Kang Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Wei WangInstitute of Respiratory Disease, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People’s Republic of ChinaTel +86 152 420 716 00Fax +86 2483282002Email wwbycmu@126.comPurpose: Cognitive impairment is an important complication of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), the main pathophysiological characteristics of OSA, is closely related to cognitive dysfunction and may be mediated by alpha-7 nicotinic acetylcholine receptors (α 7nAChR). This study investigated the effects and clarified the mechanisms of α 7nAChR on the cognitive function of mice with CIH.Methods: Thirty CD-1 mice were randomly divided into room air (RA), CIH-2 weeks (CIH2W), and CIH-4 weeks (CIH4W) groups. Cognitive function was evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests after exposure. Then, 104 CD-1 mice were exposed to CIH for 4 weeks and randomly divided into four groups: CIH4W (control), with dimethyl sulfoxide (DMSO) (sham), with α 7nAChR-specific agonist PNU-282987 (PNU), and with α 7nAChR-specific inhibitor methyllycaconitine and PNU-282987 (MLA+PNU). In addition to the evaluation of cognitive function, apoptotic bodies in the hippocampus were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, changes in p-CREB and BDNF were detected by immunohistochemistry, while those of ERK1/2, CREB, PGC-1α, FNDC5, and BDNF were detected by Western blotting in the hippocampal tissues of the mice.Results: Compared to the CIH2W and RA groups, the CIH4W group showed cognitive dysfunction in the NOR and MWM tests. The changes in cognitive dysfunction were alleviated by PNU-282987; furthermore, MLA pretreatment offset the effect. In hippocampal tissues, TUNEL assays showed decreased apoptotic cells, immunohistochemical staining showed increased expressions of p-CREB and BDNF. The expression levels of p-ERK1/2/t-ERK1/2, p-CREB/t-CREB, PGC-1α, FNDC5, and BDNF were increased after PNU-282987 injection.Conclusion: Four weeks of CIH caused cognitive dysfunction in mice. Activating α 7nAChR might ameliorate this dysfunction by upregulating the ERK1/2/CREB signaling pathway; enhancing PGC-1α, FNDC5, and BDNF expression levels; and reducing cell apoptosis in the hippocampal tissue of mice.Keywords: hypoxemia, cognitive dysfunction, nicotinic acetylcholinergic receptor alpha7 subunit, CREB, BDNF, obstructive sleep apneaShen HMeng YLiu DQin ZHuang HPan LWang WKang JDove Medical Pressarticlehypoxemiacognitive dysfunctionnicotinic acetylcholinergic receptor alpha7 subunitcrebbdnfobstructive sleep apneaPsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol Volume 13, Pp 579-590 (2021) |
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DOAJ |
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EN |
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hypoxemia cognitive dysfunction nicotinic acetylcholinergic receptor alpha7 subunit creb bdnf obstructive sleep apnea Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 |
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hypoxemia cognitive dysfunction nicotinic acetylcholinergic receptor alpha7 subunit creb bdnf obstructive sleep apnea Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 Shen H Meng Y Liu D Qin Z Huang H Pan L Wang W Kang J α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| description |
Hui Shen, Yanling Meng, Dan Liu, Zheng Qin, Hong Huang, Lei Pan, Wei Wang, Jian Kang Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Wei WangInstitute of Respiratory Disease, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People’s Republic of ChinaTel +86 152 420 716 00Fax +86 2483282002Email wwbycmu@126.comPurpose: Cognitive impairment is an important complication of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), the main pathophysiological characteristics of OSA, is closely related to cognitive dysfunction and may be mediated by alpha-7 nicotinic acetylcholine receptors (α 7nAChR). This study investigated the effects and clarified the mechanisms of α 7nAChR on the cognitive function of mice with CIH.Methods: Thirty CD-1 mice were randomly divided into room air (RA), CIH-2 weeks (CIH2W), and CIH-4 weeks (CIH4W) groups. Cognitive function was evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests after exposure. Then, 104 CD-1 mice were exposed to CIH for 4 weeks and randomly divided into four groups: CIH4W (control), with dimethyl sulfoxide (DMSO) (sham), with α 7nAChR-specific agonist PNU-282987 (PNU), and with α 7nAChR-specific inhibitor methyllycaconitine and PNU-282987 (MLA+PNU). In addition to the evaluation of cognitive function, apoptotic bodies in the hippocampus were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, changes in p-CREB and BDNF were detected by immunohistochemistry, while those of ERK1/2, CREB, PGC-1α, FNDC5, and BDNF were detected by Western blotting in the hippocampal tissues of the mice.Results: Compared to the CIH2W and RA groups, the CIH4W group showed cognitive dysfunction in the NOR and MWM tests. The changes in cognitive dysfunction were alleviated by PNU-282987; furthermore, MLA pretreatment offset the effect. In hippocampal tissues, TUNEL assays showed decreased apoptotic cells, immunohistochemical staining showed increased expressions of p-CREB and BDNF. The expression levels of p-ERK1/2/t-ERK1/2, p-CREB/t-CREB, PGC-1α, FNDC5, and BDNF were increased after PNU-282987 injection.Conclusion: Four weeks of CIH caused cognitive dysfunction in mice. Activating α 7nAChR might ameliorate this dysfunction by upregulating the ERK1/2/CREB signaling pathway; enhancing PGC-1α, FNDC5, and BDNF expression levels; and reducing cell apoptosis in the hippocampal tissue of mice.Keywords: hypoxemia, cognitive dysfunction, nicotinic acetylcholinergic receptor alpha7 subunit, CREB, BDNF, obstructive sleep apnea |
| format |
article |
| author |
Shen H Meng Y Liu D Qin Z Huang H Pan L Wang W Kang J |
| author_facet |
Shen H Meng Y Liu D Qin Z Huang H Pan L Wang W Kang J |
| author_sort |
Shen H |
| title |
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| title_short |
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| title_full |
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| title_fullStr |
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| title_full_unstemmed |
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia |
| title_sort |
α7 nicotinic acetylcholine receptor agonist pnu-282987 ameliorates cognitive impairment induced by chronic intermittent hypoxia |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/5c0d2f10ea344dc49bbc6092469d26a3 |
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