Therapeutic potential of mesenchymal stem cells on cholesterol homeostasis-associated genes in AD-like rats

Cholesterol is vital for nerve processes. Changes in cholesterol homeostasis lead to neurodegeneration and Alzheimer's disease (AD). In recent years, extensive research has confirmed the influential role of adipose tissue mesenchymal stem cells (MSCs) in managing AD. The present study aims is to investigate a new approach concerning AD by MSCs with particular reference to the cholesterol homeostasis pathway and its regulatory miRNAs in an AD-like rat model. Three groups of 24 male Wistar rats have been divided: healthy rats (control), Alzheimer's rats (AD), and Alzheimer's rats that received MSCs (AD + MSC). Cholesterol level was measured using the GC-mass technique. The mRNA and expression levels of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), apolipoprotein E (APOE), ATP-binding cassette transporter A1 (ABCA1), and CYP46A1 genes, as well as their regulating miRNAs, were assessed using real-time polymerase chain reaction (RT-PCR) and western blotting techniques, respectively. Intraventricular transplantation of MSCs improved behavioral disorders and decreased the count of Aβ plaques in brain tissue. Transplantation of these cells also led to a significant decrease in cholesterol levels and HMGCR, ApoE, and ABCA1 and a remarkable increase in CYP46A1 mRNAs and protein expression. These cells considerably changed the expression of microRNAs regulating these genes. These results indicated that the examined miRNAs could be used as promising biomarkers for AD management. Additionally, the potential therapeutic role of MSCs in improving cholesterol levels the expression levels of the targeted miRNAs and their related genes in the cholesterol homeostasis pathway was established.