Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease

Abstract The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population. To investigate mechanisms by which early life anesthesia exposure coul...

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Autores principales:	Kaley Hogarth, Ramesh Babu Vanama, Greg Stratmann, Jason T. Maynes
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/abda3efc044a41fb952dc3d8d9f3073f
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spelling	oai:doaj.org-article:abda3efc044a41fb952dc3d8d9f3073f2021-12-02T15:54:12ZSingular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease10.1038/s41598-021-85125-52045-2322https://doaj.org/article/abda3efc044a41fb952dc3d8d9f3073f2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85125-5https://doaj.org/toc/2045-2322Abstract The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population. To investigate mechanisms by which early life anesthesia exposure could induce long-term neuronal dysfunction, we exposed rats to 1 minimum alveolar concentration sevoflurane at 7 days of life. The animals were raised normally until adulthood (P300) prior to sacrifice and analysis of cortical tissue structure (TEM), mitochondrial quality control and biogenesis pathways (Western blot, ELISA, ADP/ATP content), and markers of oxidative stress, proteotoxicity and inflammation (Western blot, ELISA). We found that early life anesthesia exposure led to adverse changes in mitochondrial quality maintenance pathways, autophagy and mitochondrial biogenesis. Although there was an escalation of oxidative stress markers and an increase in the nuclear localization of stress-related transcription factors, cellular redox compensatory responses were blunted, and oxidative phosphorylation was reduced. We found upregulation of mitochondrial stress and proteotoxicity markers, but a significant reduction of mitochondrial unfolded protein response end-effectors, contributing to an increase in inflammation. Contrary to acute exposure, we did not find an increase in apoptosis. Our findings suggest that a limited, early exposure to anesthesia may produce lasting cellular dysfunction through the induction of a sustained energy deficient state, resulting in persistent neuroinflammation and altered proteostasis/toxicity, mimicking aspects of chronic neurodegenerative diseases.Kaley HogarthRamesh Babu VanamaGreg StratmannJason T. MaynesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kaley Hogarth Ramesh Babu Vanama Greg Stratmann Jason T. Maynes Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
description	Abstract The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population. To investigate mechanisms by which early life anesthesia exposure could induce long-term neuronal dysfunction, we exposed rats to 1 minimum alveolar concentration sevoflurane at 7 days of life. The animals were raised normally until adulthood (P300) prior to sacrifice and analysis of cortical tissue structure (TEM), mitochondrial quality control and biogenesis pathways (Western blot, ELISA, ADP/ATP content), and markers of oxidative stress, proteotoxicity and inflammation (Western blot, ELISA). We found that early life anesthesia exposure led to adverse changes in mitochondrial quality maintenance pathways, autophagy and mitochondrial biogenesis. Although there was an escalation of oxidative stress markers and an increase in the nuclear localization of stress-related transcription factors, cellular redox compensatory responses were blunted, and oxidative phosphorylation was reduced. We found upregulation of mitochondrial stress and proteotoxicity markers, but a significant reduction of mitochondrial unfolded protein response end-effectors, contributing to an increase in inflammation. Contrary to acute exposure, we did not find an increase in apoptosis. Our findings suggest that a limited, early exposure to anesthesia may produce lasting cellular dysfunction through the induction of a sustained energy deficient state, resulting in persistent neuroinflammation and altered proteostasis/toxicity, mimicking aspects of chronic neurodegenerative diseases.
format	article
author	Kaley Hogarth Ramesh Babu Vanama Greg Stratmann Jason T. Maynes
author_facet	Kaley Hogarth Ramesh Babu Vanama Greg Stratmann Jason T. Maynes
author_sort	Kaley Hogarth
title	Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
title_short	Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
title_full	Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
title_fullStr	Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
title_full_unstemmed	Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
title_sort	singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/abda3efc044a41fb952dc3d8d9f3073f
work_keys_str_mv	AT kaleyhogarth singularandshorttermanesthesiaexposureinthedevelopingbraininducespersistentneuronalchangesconsistentwithchronicneurodegenerativedisease AT rameshbabuvanama singularandshorttermanesthesiaexposureinthedevelopingbraininducespersistentneuronalchangesconsistentwithchronicneurodegenerativedisease AT gregstratmann singularandshorttermanesthesiaexposureinthedevelopingbraininducespersistentneuronalchangesconsistentwithchronicneurodegenerativedisease AT jasontmaynes singularandshorttermanesthesiaexposureinthedevelopingbraininducespersistentneuronalchangesconsistentwithchronicneurodegenerativedisease
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Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease

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