Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Abstract Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration...

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Autores principales:	Patricia Soriano Roque, Mehdi Hooshmandi, Laura Neagu-Lund, Shelly Yin, Noosha Yousefpour, Hiroaki Sato, Tamaki Sato, Yosuke Nakadate, Akiko Kawakami, Soroush Tahmasebi, Alfredo Ribeiro-da-Silva, Christos G. Gkogkas, Masha Prager-Khoutorsky, Thomas Schricker, Linda Wykes, Arkady Khoutorsky
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cbe67007926647f3be7184e7fde402e4
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spelling	oai:doaj.org-article:cbe67007926647f3be7184e7fde402e42021-12-02T18:46:55ZIntranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC110.1038/s41598-021-94849-32045-2322https://doaj.org/article/cbe67007926647f3be7184e7fde402e42021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94849-3https://doaj.org/toc/2045-2322Abstract Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.Patricia Soriano RoqueMehdi HooshmandiLaura Neagu-LundShelly YinNoosha YousefpourHiroaki SatoTamaki SatoYosuke NakadateAkiko KawakamiSoroush TahmasebiAlfredo Ribeiro-da-SilvaChristos G. GkogkasMasha Prager-KhoutorskyThomas SchrickerLinda WykesArkady KhoutorskyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patricia Soriano Roque Mehdi Hooshmandi Laura Neagu-Lund Shelly Yin Noosha Yousefpour Hiroaki Sato Tamaki Sato Yosuke Nakadate Akiko Kawakami Soroush Tahmasebi Alfredo Ribeiro-da-Silva Christos G. Gkogkas Masha Prager-Khoutorsky Thomas Schricker Linda Wykes Arkady Khoutorsky Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
description	Abstract Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.
format	article
author	Patricia Soriano Roque Mehdi Hooshmandi Laura Neagu-Lund Shelly Yin Noosha Yousefpour Hiroaki Sato Tamaki Sato Yosuke Nakadate Akiko Kawakami Soroush Tahmasebi Alfredo Ribeiro-da-Silva Christos G. Gkogkas Masha Prager-Khoutorsky Thomas Schricker Linda Wykes Arkady Khoutorsky
author_facet	Patricia Soriano Roque Mehdi Hooshmandi Laura Neagu-Lund Shelly Yin Noosha Yousefpour Hiroaki Sato Tamaki Sato Yosuke Nakadate Akiko Kawakami Soroush Tahmasebi Alfredo Ribeiro-da-Silva Christos G. Gkogkas Masha Prager-Khoutorsky Thomas Schricker Linda Wykes Arkady Khoutorsky
author_sort	Patricia Soriano Roque
title	Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
title_short	Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
title_full	Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
title_fullStr	Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
title_full_unstemmed	Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
title_sort	intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mtorc1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cbe67007926647f3be7184e7fde402e4
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Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

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