Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer’s Disease Mice via Transcriptomic and Cellular Analysis

Abstract

Alzheimer’s disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer’s disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer’s disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer’s disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue.

Role of the Insulin-like Growth Factor System in Neurodegenerative Disease

“…Somewhat paradoxically, when crossed with mice with liver-specific IGF-I deficiency, and therefore reduced endocrine IGF-I, mice with APP/PSEN1 mutations have earlier Aβ accumulation [58]. Furthermore, IGF-I delivered subcutaneously reduces Aβ overexpression in the cortex and hippocampus [59], increases brain Aβ complexed with carrier proteins [61], and improves behavioural patterns [60,61]. Subcutaneous IGF-I also reduces Aβ accumulation in rats administered Aβ intracerebroventricularly [66].…”