Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining le...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/391 |
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| author | Nerea Jimenez-Tellez Marcus Pehar Fahad Iqbal Alberto Casas-Ortiz Tiffany Rice Naweed I. Syed |
| author_facet | Nerea Jimenez-Tellez Marcus Pehar Fahad Iqbal Alberto Casas-Ortiz Tiffany Rice Naweed I. Syed |
| author_sort | Nerea Jimenez-Tellez |
| collection | DOAJ |
| description | Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining learning and memory in freely behaving animals, and in vitro using cultured neurons to assess its impact on viability, mitochondrial structure, and function. We demonstrate here that neonatal exposure to sub-clinically used concentrations of SEV results in significant, albeit subtle and previously unreported, learning and memory deficits in adult animals. These deficits involve neuronal cell death, as observed in cell culture, and are likely mediated through perturbed mitochondrial structure and function. Parenthetically, both behavioural deficits and cell death were prevented when the animals and cultured neurons were pre-treated with the anesthetic adjuvant Dexmedetomidine (DEX). Taken together, our data provide direct evidence for sevoflurane-induced cytotoxic effects at the neuronal level while perturbing learning and memory at the behavioural level. In addition, our data underscore the importance of adjuvant agents such as DEX that could potentially counter the harmful effects of commonly used anesthetic agents for better clinical outcomes. |
| first_indexed | 2024-03-11T09:07:25Z |
| format | Article |
| id | doaj.art-dd0a5846ca67496f995b1ad918633c8d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:25Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-dd0a5846ca67496f995b1ad918633c8d2023-11-16T19:17:32ZengMDPI AGBiomedicines2227-90592023-01-0111239110.3390/biomedicines11020391Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult AnimalsNerea Jimenez-Tellez0Marcus Pehar1Fahad Iqbal2Alberto Casas-Ortiz3Tiffany Rice4Naweed I. Syed5Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 4N1, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 4N1, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, CanadaAnesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining learning and memory in freely behaving animals, and in vitro using cultured neurons to assess its impact on viability, mitochondrial structure, and function. We demonstrate here that neonatal exposure to sub-clinically used concentrations of SEV results in significant, albeit subtle and previously unreported, learning and memory deficits in adult animals. These deficits involve neuronal cell death, as observed in cell culture, and are likely mediated through perturbed mitochondrial structure and function. Parenthetically, both behavioural deficits and cell death were prevented when the animals and cultured neurons were pre-treated with the anesthetic adjuvant Dexmedetomidine (DEX). Taken together, our data provide direct evidence for sevoflurane-induced cytotoxic effects at the neuronal level while perturbing learning and memory at the behavioural level. In addition, our data underscore the importance of adjuvant agents such as DEX that could potentially counter the harmful effects of commonly used anesthetic agents for better clinical outcomes.https://www.mdpi.com/2227-9059/11/2/391sevofluranedexmedetomidineanestheticslearning and memorymitochondria |
| spellingShingle | Nerea Jimenez-Tellez Marcus Pehar Fahad Iqbal Alberto Casas-Ortiz Tiffany Rice Naweed I. Syed Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals Biomedicines sevoflurane dexmedetomidine anesthetics learning and memory mitochondria |
| title | Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals |
| title_full | Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals |
| title_fullStr | Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals |
| title_full_unstemmed | Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals |
| title_short | Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals |
| title_sort | dexmedetomidine pre treatment of neonatal rats prevents sevoflurane induced deficits in learning and memory in the adult animals |
| topic | sevoflurane dexmedetomidine anesthetics learning and memory mitochondria |
| url | https://www.mdpi.com/2227-9059/11/2/391 |
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