Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage
The beta-3 adrenergic receptor (β3-AR), whose expression is modulated by oxygen levels, was found to play a key role in organ maturation, and its agonism was reported to mitigate hyperoxia-induced large bowel damage by preventing organ hypoplasia, preserving epithelial integrity, vascularization, an...
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2025-03-01
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| author | Patrizia Nardini Luca Filippi Virginia Zizi Marta Molino Camilla Fazi Matteo Chivetti Alessandro Pini |
| author_facet | Patrizia Nardini Luca Filippi Virginia Zizi Marta Molino Camilla Fazi Matteo Chivetti Alessandro Pini |
| author_sort | Patrizia Nardini |
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| description | The beta-3 adrenergic receptor (β3-AR), whose expression is modulated by oxygen levels, was found to play a key role in organ maturation, and its agonism was reported to mitigate hyperoxia-induced large bowel damage by preventing organ hypoplasia, preserving epithelial integrity, vascularization, and the neurochemical coding in the colonic myenteric plexus. This study explored the effects of β3-AR agonism in preventing hyperoxia-related alterations on the ileal enteric nervous system (ENS). Sprague–Dawley rat pups were reared under normoxia or hyperoxia (85%) during the first two weeks after birth and treated or not with the β3-AR agonist BRL37344 at 1, 3, or 6 mg/kg. Hyperoxia caused an imbalance of inhibitory nitrergic and excitatory cholinergic neurons in both the myenteric and submucosal plexuses and decreased the amounts of neurons in the submucosal plexus and that of S100β<sup>+</sup> and GFAP<sup>+</sup> glial cells in the myenteric plexus. Administration of 3 mg/kg BRL37344 preserved the neuronal chemical coding and partially prevented the loss of myenteric GFAP<sup>+</sup> glial cells, while it did not counteract submucosal neuronal loss. Our findings indicate the potential of β3-AR agonism as a new therapeutic strategy for hyperoxia-induced ileal ENS alterations. |
| format | Article |
| id | doaj-art-ae7ef981f91e45b9b4a1c738f2676c12 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-ae7ef981f91e45b9b4a1c738f2676c122025-08-20T02:17:00ZengMDPI AGCells2073-44092025-03-0114747510.3390/cells14070475Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced DamagePatrizia Nardini0Luca Filippi1Virginia Zizi2Marta Molino3Camilla Fazi4Matteo Chivetti5Alessandro Pini6Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyNeonatology and Neonatal Intensive Care Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyDepartment of Pediatric, Meyer Children’s University Hospital, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyThe beta-3 adrenergic receptor (β3-AR), whose expression is modulated by oxygen levels, was found to play a key role in organ maturation, and its agonism was reported to mitigate hyperoxia-induced large bowel damage by preventing organ hypoplasia, preserving epithelial integrity, vascularization, and the neurochemical coding in the colonic myenteric plexus. This study explored the effects of β3-AR agonism in preventing hyperoxia-related alterations on the ileal enteric nervous system (ENS). Sprague–Dawley rat pups were reared under normoxia or hyperoxia (85%) during the first two weeks after birth and treated or not with the β3-AR agonist BRL37344 at 1, 3, or 6 mg/kg. Hyperoxia caused an imbalance of inhibitory nitrergic and excitatory cholinergic neurons in both the myenteric and submucosal plexuses and decreased the amounts of neurons in the submucosal plexus and that of S100β<sup>+</sup> and GFAP<sup>+</sup> glial cells in the myenteric plexus. Administration of 3 mg/kg BRL37344 preserved the neuronal chemical coding and partially prevented the loss of myenteric GFAP<sup>+</sup> glial cells, while it did not counteract submucosal neuronal loss. Our findings indicate the potential of β3-AR agonism as a new therapeutic strategy for hyperoxia-induced ileal ENS alterations.https://www.mdpi.com/2073-4409/14/7/475BRL37344beta-3 adrenoceptorbeta-3 adrenoceptor agonismdevelopmenthyperoxiaileum |
| spellingShingle | Patrizia Nardini Luca Filippi Virginia Zizi Marta Molino Camilla Fazi Matteo Chivetti Alessandro Pini Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage Cells BRL37344 beta-3 adrenoceptor beta-3 adrenoceptor agonism development hyperoxia ileum |
| title | Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage |
| title_full | Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage |
| title_fullStr | Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage |
| title_full_unstemmed | Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage |
| title_short | Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage |
| title_sort | beta 3 adrenoceptor agonism protects the enteric nervous tissue against hyperoxia induced damage |
| topic | BRL37344 beta-3 adrenoceptor beta-3 adrenoceptor agonism development hyperoxia ileum |
| url | https://www.mdpi.com/2073-4409/14/7/475 |
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