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Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results in intellectual disability and, in ∼50% of patients, autism spectrum disorder. The protein products that are altered in TSC (TSC1 and TSC2) form a complex to inhibit the mammalian target of rapamycin [mTOR; mTOR complex...

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Autores principales: Saré, Rachel Michelle, Torossian, Anita, Loutaev, Inna, Smith, Carolyn Beebe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347307/
https://www.ncbi.nlm.nih.gov/pubmed/35851298
http://dx.doi.org/10.1523/ENEURO.0480-21.2022
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author Saré, Rachel Michelle
Torossian, Anita
Loutaev, Inna
Smith, Carolyn Beebe
author_facet Saré, Rachel Michelle
Torossian, Anita
Loutaev, Inna
Smith, Carolyn Beebe
author_sort Saré, Rachel Michelle
collection PubMed
description Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results in intellectual disability and, in ∼50% of patients, autism spectrum disorder. The protein products that are altered in TSC (TSC1 and TSC2) form a complex to inhibit the mammalian target of rapamycin [mTOR; mTOR complex 1 (mTORC1)] pathway. This pathway has been shown to affect the process of mRNA translation through its action on ribosomal protein S6 and 4-elongation binding protein 1. It is thought that mutations in the TSC proteins lead to upregulation of the mTORC1 pathway and consequently an increase in protein synthesis. Unexpectedly, our previous study of a mouse model of TSC (Tsc2(Djk)(+/−)) demonstrated decreased in vivo rates of protein synthesis throughout the brain. In the present study, we confirm those results in another Tsc2(+/−) mouse model, one with a different mutation locus and on a mixed background (Tsc2(Mjg)(+/−)). We also examine mTORC1 signaling and possible effects of prior isoflurane anesthesia. Because measurements of protein synthesis rates in vivo require surgical preparation of the animal and anesthesia, we examine mTORC1 signaling pathways both under baseline conditions and following recovery from anesthesia. Our results demonstrate regionally selective effects of prior anesthesia. Overall, our results in both in vivo models suggest divergences from the central hypothesis regarding TSC and show the importance of studying protein synthesis in vivo.
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spelling pubmed-93473072022-08-04 Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex Saré, Rachel Michelle Torossian, Anita Loutaev, Inna Smith, Carolyn Beebe eNeuro Research Article: Confirmation Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results in intellectual disability and, in ∼50% of patients, autism spectrum disorder. The protein products that are altered in TSC (TSC1 and TSC2) form a complex to inhibit the mammalian target of rapamycin [mTOR; mTOR complex 1 (mTORC1)] pathway. This pathway has been shown to affect the process of mRNA translation through its action on ribosomal protein S6 and 4-elongation binding protein 1. It is thought that mutations in the TSC proteins lead to upregulation of the mTORC1 pathway and consequently an increase in protein synthesis. Unexpectedly, our previous study of a mouse model of TSC (Tsc2(Djk)(+/−)) demonstrated decreased in vivo rates of protein synthesis throughout the brain. In the present study, we confirm those results in another Tsc2(+/−) mouse model, one with a different mutation locus and on a mixed background (Tsc2(Mjg)(+/−)). We also examine mTORC1 signaling and possible effects of prior isoflurane anesthesia. Because measurements of protein synthesis rates in vivo require surgical preparation of the animal and anesthesia, we examine mTORC1 signaling pathways both under baseline conditions and following recovery from anesthesia. Our results demonstrate regionally selective effects of prior anesthesia. Overall, our results in both in vivo models suggest divergences from the central hypothesis regarding TSC and show the importance of studying protein synthesis in vivo. Society for Neuroscience 2022-08-01 /pmc/articles/PMC9347307/ /pubmed/35851298 http://dx.doi.org/10.1523/ENEURO.0480-21.2022 Text en Copyright © 2022 Saré et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: Confirmation
Saré, Rachel Michelle
Torossian, Anita
Loutaev, Inna
Smith, Carolyn Beebe
Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title_full Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title_fullStr Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title_full_unstemmed Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title_short Confirmation of Decreased Rates of Cerebral Protein Synthesis In Vivo in a Mouse Model of Tuberous Sclerosis Complex
title_sort confirmation of decreased rates of cerebral protein synthesis in vivo in a mouse model of tuberous sclerosis complex
topic Research Article: Confirmation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347307/
https://www.ncbi.nlm.nih.gov/pubmed/35851298
http://dx.doi.org/10.1523/ENEURO.0480-21.2022
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