Adipose tissue‐derived mesenchymal stem cells ameliorate cognitive impairment in Alzheimer's disease rat model: Emerging role of SIRT1

Abstract

Alzheimer's disease (AD) is a complex form of neurodegenerative dementia. Growing body of evidence supports the cardinal role of sirtuin1 (SIRT1) in neurodegeneration and AD development. Recently, adipose tissue‐derived mesenchymal stem cells (Ad‐MSCs) have made their mark for a wide array of regenerative medicine applications, including neurodegenerative disorders. Therefore, the present study aimed to investigate the therapeutic potential of Ad‐MSCs in AD rat model, and to explore the possible implication of SIRT1. Ad‐MSCs were isolated from rat epididymal fat pads and properly characterized. Aluminum chloride was used to induce AD in rats, and afterward, a group of AD‐induced rats received a single dose of Ad‐MSCs (2 × 106 cell, I.V per rat). One month after Ad‐MSCs transplantation, behavioral tests were done, brain tissues were collected, then histopathological and biochemical assessments were performed. Amyloid beta and SIRT1 levels were determined by enzyme‐linked immunosorbent assay. Whereas expression levels of neprilysin, BCL2 associated X protein, B‐cell lymphoma‐2, interleukin‐1β, interleukin‐6, and nerve growth factor in hippocampus and frontal cortex brain tissues were assessed using reverse transcriptase quantitative polymerase chain reaction. Our data demonstrated that transplantation of Ad‐MSCs alleviated cognitive impairment in AD rats. Additionally, they exhibited anti‐amyloidogenic, antiapoptotic, anti‐inflammatory, as well as neurogenic effects. Furthermore, Ad‐MSCs were found to possibly mediate their therapeutic effects, at least partially, via modulating both central and systemic SIRT1 levels. Hence, the current study portrays Ad‐MSCs as an effective therapeutic approach for AD management and opens the door for future investigations to further elucidate the role of SIRT1 and its interrelated molecular mediators in AD.

Neuro-Adipokine Crosstalk in Alzheimer’s Disease

“…The pro-inflammatory ADSCs can increase neuroinflammation by inducing proliferation and differentiation of CD4+ and CD8+ T cells [ 17 ]. Transplantation of ADSCs into a rat model of AD ameliorates cognitive impairments, enhances Aβ clearance, and suppresses apoptosis and neuroinflammation by modulating central and systemic SIRT1 levels [ 18 , 19 ]. Intraventricular injection of ADSCs has been shown to improve AD pathogenesis by modulating central cholesterol homeostasis [ 20 ].…”