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Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring

Prenatal exposure to anesthetics has raised increasing attention about the neuronal development in offspring. Animal models are usually used for investigation. As a new drug, esketamine is the s-isoform of ketamine and is twice as potent as the racemic ketamine with less reported adverse effects. Es...

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Autores principales: Huang, Ronghua, Lin, Bingbiao, Tian, Hongyan, Luo, Qichen, Li, Yalan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333374/
https://www.ncbi.nlm.nih.gov/pubmed/37119312
http://dx.doi.org/10.1007/s10571-023-01354-4
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author Huang, Ronghua
Lin, Bingbiao
Tian, Hongyan
Luo, Qichen
Li, Yalan
author_facet Huang, Ronghua
Lin, Bingbiao
Tian, Hongyan
Luo, Qichen
Li, Yalan
author_sort Huang, Ronghua
collection PubMed
description Prenatal exposure to anesthetics has raised increasing attention about the neuronal development in offspring. Animal models are usually used for investigation. As a new drug, esketamine is the s-isoform of ketamine and is twice as potent as the racemic ketamine with less reported adverse effects. Esketamine is currently being used and become more favorable in clinical anesthesia work, including surgeries during pregnancy, yet the effect on the offspring is unknown. The present study aimed to elucidate the effects of gestational administration of esketamine on neuronal development in offspring, using a rat model. Gestational day 14.5 pregnant rats received intravenous injections of esketamine. The postnatal day 0 (P0) hippocampus was digested and cultured in vitro to display the neuronal growth morphology. On Day 4 the in vitro experiments revealed a shorter axon length and fewer dendrite branches in the esketamine group. The results from the EdU- imaging kit showed decreased proliferative capacity in the subventricular zone (SVZ) and dentate gyrus (DG) in both P0 and P30 offspring brains in the esketamine group. Moreover, neurogenesis, neuron maturity and spine density were impaired, resulting in attenuated long-term potentiation (LTP). Compromised hippocampal function accounted for the deficits in neuronal cognition, memory and emotion. The evidence obtained suggests that the neurobehavioral deficit due to prenatal exposure to esketamine may be related to the decrease phosphorylation of CREB and abnormalities in N-methyl-d-aspartic acid receptor subunits. Taken together, these results demonstrate the negative effect of prenatal esketamine exposure on neuronal development in offspring rats. GRAPHICAL ABSTRACT: G14.5 esketamine administration influenced the neurobehavior of the offspring in adolescence. Poorer neuronal growth and reduced brain proliferative capacity in late gestation and juvenile pups resulted in impaired P30 neuronal plasticity and synaptic spines as well as abnormalities in NMDAR subunits. Attenuated LTP reflected compromised hippocampal function, as confirmed by behavioral tests of cognition, memory and emotions. This figure was completed on the website of Figdraw. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-023-01354-4.
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spelling pubmed-103333742023-07-12 Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring Huang, Ronghua Lin, Bingbiao Tian, Hongyan Luo, Qichen Li, Yalan Cell Mol Neurobiol Original Research Prenatal exposure to anesthetics has raised increasing attention about the neuronal development in offspring. Animal models are usually used for investigation. As a new drug, esketamine is the s-isoform of ketamine and is twice as potent as the racemic ketamine with less reported adverse effects. Esketamine is currently being used and become more favorable in clinical anesthesia work, including surgeries during pregnancy, yet the effect on the offspring is unknown. The present study aimed to elucidate the effects of gestational administration of esketamine on neuronal development in offspring, using a rat model. Gestational day 14.5 pregnant rats received intravenous injections of esketamine. The postnatal day 0 (P0) hippocampus was digested and cultured in vitro to display the neuronal growth morphology. On Day 4 the in vitro experiments revealed a shorter axon length and fewer dendrite branches in the esketamine group. The results from the EdU- imaging kit showed decreased proliferative capacity in the subventricular zone (SVZ) and dentate gyrus (DG) in both P0 and P30 offspring brains in the esketamine group. Moreover, neurogenesis, neuron maturity and spine density were impaired, resulting in attenuated long-term potentiation (LTP). Compromised hippocampal function accounted for the deficits in neuronal cognition, memory and emotion. The evidence obtained suggests that the neurobehavioral deficit due to prenatal exposure to esketamine may be related to the decrease phosphorylation of CREB and abnormalities in N-methyl-d-aspartic acid receptor subunits. Taken together, these results demonstrate the negative effect of prenatal esketamine exposure on neuronal development in offspring rats. GRAPHICAL ABSTRACT: G14.5 esketamine administration influenced the neurobehavior of the offspring in adolescence. Poorer neuronal growth and reduced brain proliferative capacity in late gestation and juvenile pups resulted in impaired P30 neuronal plasticity and synaptic spines as well as abnormalities in NMDAR subunits. Attenuated LTP reflected compromised hippocampal function, as confirmed by behavioral tests of cognition, memory and emotions. This figure was completed on the website of Figdraw. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-023-01354-4. Springer US 2023-04-29 2023 /pmc/articles/PMC10333374/ /pubmed/37119312 http://dx.doi.org/10.1007/s10571-023-01354-4 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Huang, Ronghua
Lin, Bingbiao
Tian, Hongyan
Luo, Qichen
Li, Yalan
Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title_full Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title_fullStr Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title_full_unstemmed Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title_short Prenatal Exposure to General Anesthesia Drug Esketamine Impaired Neurobehavior in Offspring
title_sort prenatal exposure to general anesthesia drug esketamine impaired neurobehavior in offspring
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333374/
https://www.ncbi.nlm.nih.gov/pubmed/37119312
http://dx.doi.org/10.1007/s10571-023-01354-4
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