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Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity
Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer’s disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with β-amyloid (Aβ) load are critical in generating cognitive deficits. Th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865153/ https://www.ncbi.nlm.nih.gov/pubmed/29572520 http://dx.doi.org/10.1038/s41598-018-22985-4 |
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author | Amtul, Zareen Hill, David J. Arany, Edith J. Cechetto, David F. |
author_facet | Amtul, Zareen Hill, David J. Arany, Edith J. Cechetto, David F. |
author_sort | Amtul, Zareen |
collection | PubMed |
description | Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer’s disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with β-amyloid (Aβ) load are critical in generating cognitive deficits. These cognitive deficits are likely to be associated with impaired insulin signaling. In this study, we examined the histological presence of insulin-like growth factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct brain circuits compared with morphological brain damage in a co-morbid rat model of striatal ischemia (ET1) and Aβ toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Aβ + ET1 rats, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion. These regions included subcortical white matter, motor cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region and horizontal diagonal band of Broca in the basal forebrain. The alteration in IGF-1 and IRS-1 presence induced by ET1 or Aβ rats alone was not severe enough to affect the entire brain circuit. Understanding the causal or etiologic interaction between insulin and IGF signaling and co-morbidity after ischemia and Aβ toxicity will help design more effective therapeutics. |
format | Online Article Text |
id | pubmed-5865153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58651532018-03-27 Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity Amtul, Zareen Hill, David J. Arany, Edith J. Cechetto, David F. Sci Rep Article Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer’s disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with β-amyloid (Aβ) load are critical in generating cognitive deficits. These cognitive deficits are likely to be associated with impaired insulin signaling. In this study, we examined the histological presence of insulin-like growth factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct brain circuits compared with morphological brain damage in a co-morbid rat model of striatal ischemia (ET1) and Aβ toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Aβ + ET1 rats, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion. These regions included subcortical white matter, motor cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region and horizontal diagonal band of Broca in the basal forebrain. The alteration in IGF-1 and IRS-1 presence induced by ET1 or Aβ rats alone was not severe enough to affect the entire brain circuit. Understanding the causal or etiologic interaction between insulin and IGF signaling and co-morbidity after ischemia and Aβ toxicity will help design more effective therapeutics. Nature Publishing Group UK 2018-03-23 /pmc/articles/PMC5865153/ /pubmed/29572520 http://dx.doi.org/10.1038/s41598-018-22985-4 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Amtul, Zareen Hill, David J. Arany, Edith J. Cechetto, David F. Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title | Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title_full | Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title_fullStr | Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title_full_unstemmed | Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title_short | Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity |
title_sort | altered insulin/insulin-like growth factor signaling in a comorbid rat model of ischemia and β-amyloid toxicity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865153/ https://www.ncbi.nlm.nih.gov/pubmed/29572520 http://dx.doi.org/10.1038/s41598-018-22985-4 |
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