A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly
Abstract Anesthetics are deemed necessary for all major surgical procedures. However, they have also been found to exert neurotoxic effects when tested on various experimental models, but the underlying mechanisms remain unknown. Earlier studies have implicated mitochondrial fragmentation as a poten...
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2021
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oai:doaj.org-article:20e0a4bcdfa64b8aa41c63f3685cf0502021-12-02T13:20:04ZA synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly10.1038/s41598-021-84168-y2045-2322https://doaj.org/article/20e0a4bcdfa64b8aa41c63f3685cf0502021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84168-yhttps://doaj.org/toc/2045-2322Abstract Anesthetics are deemed necessary for all major surgical procedures. However, they have also been found to exert neurotoxic effects when tested on various experimental models, but the underlying mechanisms remain unknown. Earlier studies have implicated mitochondrial fragmentation as a potential target of anesthetic-induced toxicity, although clinical strategies to protect their structure and function remain sparse. Here, we sought to determine if preserving mitochondrial networks with a non-toxic, short-life synthetic peptide—P110, would protect cortical neurons against both inhalational and intravenous anesthetic-induced neurotoxicity. This study provides the first direct and comparative account of three key anesthetics (desflurane, propofol, and ketamine) when used under identical conditions, and demonstrates their impact on neonatal, rat cortical neuronal viability, neurite outgrowth and synaptic assembly. Furthermore, we discovered that inhibiting Fis1-mediated mitochondrial fission reverses anesthetic-induced aberrations in an agent-specific manner. This study underscores the importance of designing mitigation strategies invoking mitochondria-mediated protection from anesthetic-induced toxicity in both animals and humans.Fahad IqbalMarcus PeharAndrew J. ThompsonUrva AzeemKiana JahanbakhshNerea Jimenez-TellezRasha SabounyShadab BatoolAtika SyedaJennifer ChowPranav MachirajuTimothy ShuttKamran YusufJane ShearerTiffany RiceNaweed I. SyedNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
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Medicine R Science Q Fahad Iqbal Marcus Pehar Andrew J. Thompson Urva Azeem Kiana Jahanbakhsh Nerea Jimenez-Tellez Rasha Sabouny Shadab Batool Atika Syeda Jennifer Chow Pranav Machiraju Timothy Shutt Kamran Yusuf Jane Shearer Tiffany Rice Naweed I. Syed A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| description |
Abstract Anesthetics are deemed necessary for all major surgical procedures. However, they have also been found to exert neurotoxic effects when tested on various experimental models, but the underlying mechanisms remain unknown. Earlier studies have implicated mitochondrial fragmentation as a potential target of anesthetic-induced toxicity, although clinical strategies to protect their structure and function remain sparse. Here, we sought to determine if preserving mitochondrial networks with a non-toxic, short-life synthetic peptide—P110, would protect cortical neurons against both inhalational and intravenous anesthetic-induced neurotoxicity. This study provides the first direct and comparative account of three key anesthetics (desflurane, propofol, and ketamine) when used under identical conditions, and demonstrates their impact on neonatal, rat cortical neuronal viability, neurite outgrowth and synaptic assembly. Furthermore, we discovered that inhibiting Fis1-mediated mitochondrial fission reverses anesthetic-induced aberrations in an agent-specific manner. This study underscores the importance of designing mitigation strategies invoking mitochondria-mediated protection from anesthetic-induced toxicity in both animals and humans. |
| format |
article |
| author |
Fahad Iqbal Marcus Pehar Andrew J. Thompson Urva Azeem Kiana Jahanbakhsh Nerea Jimenez-Tellez Rasha Sabouny Shadab Batool Atika Syeda Jennifer Chow Pranav Machiraju Timothy Shutt Kamran Yusuf Jane Shearer Tiffany Rice Naweed I. Syed |
| author_facet |
Fahad Iqbal Marcus Pehar Andrew J. Thompson Urva Azeem Kiana Jahanbakhsh Nerea Jimenez-Tellez Rasha Sabouny Shadab Batool Atika Syeda Jennifer Chow Pranav Machiraju Timothy Shutt Kamran Yusuf Jane Shearer Tiffany Rice Naweed I. Syed |
| author_sort |
Fahad Iqbal |
| title |
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| title_short |
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| title_full |
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| title_fullStr |
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| title_full_unstemmed |
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| title_sort |
synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/20e0a4bcdfa64b8aa41c63f3685cf050 |
| work_keys_str_mv |
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