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Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats
As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory proces...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576226/ https://www.ncbi.nlm.nih.gov/pubmed/32852134 http://dx.doi.org/10.1111/acel.13220 |
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author | Frazier, Hilaree N. Anderson, Katie L. Ghoweri, Adam O. Lin, Ruei-Lung Hawkinson, Tara R. Popa, Gabriel J. Sompol, Pradoldej Mendenhall, Michael D. Norris, Christopher M. Thibault, Olivier |
author_facet | Frazier, Hilaree N. Anderson, Katie L. Ghoweri, Adam O. Lin, Ruei-Lung Hawkinson, Tara R. Popa, Gabriel J. Sompol, Pradoldej Mendenhall, Michael D. Norris, Christopher M. Thibault, Olivier |
author_sort | Frazier, Hilaree N. |
collection | PubMed |
description | As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome measures, including Morris water maze and ambulatory gait performance, immunofluorescence, immunohistochemistry, and Western immunoblotting. In aged animals, the IRβ construct was associated with enhanced performance on the Morris water maze task, suggesting that this receptor was able to improve memory recall. Additionally, in both age‐groups, a reduced stride length was noted in IRβ‐treated animals along with elevated hippocampal insulin receptor levels. These results provide new insights into the potential impact of increasing neuronal insulin signaling in the hippocampus of aged animals and support the efficacy of molecularly elevating insulin receptor activity in vivo in the absence of the ligand to directly study this process. |
format | Online Article Text |
id | pubmed-7576226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75762262020-10-23 Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats Frazier, Hilaree N. Anderson, Katie L. Ghoweri, Adam O. Lin, Ruei-Lung Hawkinson, Tara R. Popa, Gabriel J. Sompol, Pradoldej Mendenhall, Michael D. Norris, Christopher M. Thibault, Olivier Aging Cell Original Articles As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome measures, including Morris water maze and ambulatory gait performance, immunofluorescence, immunohistochemistry, and Western immunoblotting. In aged animals, the IRβ construct was associated with enhanced performance on the Morris water maze task, suggesting that this receptor was able to improve memory recall. Additionally, in both age‐groups, a reduced stride length was noted in IRβ‐treated animals along with elevated hippocampal insulin receptor levels. These results provide new insights into the potential impact of increasing neuronal insulin signaling in the hippocampus of aged animals and support the efficacy of molecularly elevating insulin receptor activity in vivo in the absence of the ligand to directly study this process. John Wiley and Sons Inc. 2020-08-27 2020-10 /pmc/articles/PMC7576226/ /pubmed/32852134 http://dx.doi.org/10.1111/acel.13220 Text en © 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Frazier, Hilaree N. Anderson, Katie L. Ghoweri, Adam O. Lin, Ruei-Lung Hawkinson, Tara R. Popa, Gabriel J. Sompol, Pradoldej Mendenhall, Michael D. Norris, Christopher M. Thibault, Olivier Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title | Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title_full | Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title_fullStr | Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title_full_unstemmed | Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title_short | Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats |
title_sort | molecular elevation of insulin receptor signaling improves memory recall in aged fischer 344 rats |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576226/ https://www.ncbi.nlm.nih.gov/pubmed/32852134 http://dx.doi.org/10.1111/acel.13220 |
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