Anatomy and Cell Biology Publications
Title
Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and beta-Amyloid Toxicity
Document Type
Article
Publication Date
3-23-2018
Issue
1
Journal
Scientific Reports
Volume
8
First Page
5136
URL with Digital Object Identifier
https://doi.org/10.1038/s41598-018-22985-4
Abstract
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 beta-amyloid (A beta) 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 A beta toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in A beta + 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 A beta 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 A beta toxicity will help design more effective therapeutics.
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