Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis
Abstract Background Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-06-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51558 |
| _version_ | 1818545617733943296 |
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| author | Jian‐Bo Lin Nan‐Long Lin Xu Li Ming‐Qiang Kang |
| author_facet | Jian‐Bo Lin Nan‐Long Lin Xu Li Ming‐Qiang Kang |
| author_sort | Jian‐Bo Lin |
| collection | DOAJ |
| description | Abstract Background Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH. Methods The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1. Results In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1‐treated mice. Conclusion Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1. |
| first_indexed | 2024-12-12T07:42:27Z |
| format | Article |
| id | doaj.art-ae42f6dc4a674ffab2038c3ee1793eda |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-12T07:42:27Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-ae42f6dc4a674ffab2038c3ee1793eda2022-12-22T00:32:45ZengWileyAnnals of Clinical and Translational Neurology2328-95032022-06-019678679410.1002/acn3.51558Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosisJian‐Bo Lin0Nan‐Long Lin1Xu Li2Ming‐Qiang Kang3Department of Thoracic Surgery First Affiliated Hospital of Fujian Medical University No. 20 Chazhong Road Fuzhou Fujian 350005 ChinaDepartment of Thoracic Surgery First Affiliated Hospital of Fujian Medical University No. 20 Chazhong Road Fuzhou Fujian 350005 ChinaDepartment of Thoracic Surgery First Affiliated Hospital of Fujian Medical University No. 20 Chazhong Road Fuzhou Fujian 350005 ChinaDepartment of Thoracic Surgery Fujian Medical University Union Hospital No. 29 Xinquan Road, Gulou District Fuzhou Fujian 350001 ChinaAbstract Background Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH. Methods The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1. Results In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1‐treated mice. Conclusion Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1.https://doi.org/10.1002/acn3.51558 |
| spellingShingle | Jian‐Bo Lin Nan‐Long Lin Xu Li Ming‐Qiang Kang Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis Annals of Clinical and Translational Neurology |
| title | Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| title_full | Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| title_fullStr | Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| title_full_unstemmed | Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| title_short | Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| title_sort | antagonist of chrna1 prevents the pathogenesis of primary focal hyperhidrosis |
| url | https://doi.org/10.1002/acn3.51558 |
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