Adipose-Derived Mesenchymal Stem Cells Partially Compensating the Neurodegenerative Signs at The Behavioral, Physiological, and Molecular Levels in AD Rat Model

Emad M Elzayat,Yasmine Elbeltagy,Fatma Mohamed,Asmaa Husein,Mohamed Hosney

doi:10.21608/eajbsd.2021.200376

Abstract

Alzheimer's disease (AD) is the most common form of dementia. Due to the multifaceted nature of AD pathology and limited understanding of its etiology, AD is difficult to be treated with currently available pharmaceuticals. Recent studies suggest that transplantation of mesenchymal stem cells might have therapeutic potential on several neurodegenerative disorders. In addition, it can ameliorate neuropathological deficits and physiological disorders in AD. The current study aims to evaluate the potential therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in AD rat model after the induction with AlCl3. After the induction phase, labeled ADMSCs have been injected intravenously. Open-field behavioral tests were conducted, serum β-amyloid levels, cholinesterase activity, and brain antioxidant status were evaluated. Besides, the expression of apoptotic and necrotic markers was quantified via RT-qPCR in brain tissues. Histopathological alterations in the brain were examined as well. Signs of dementia as manifested by behavioral tests have been recorded in AD rats, accumulation of β-amyloid in blood, reduced serum cholinesterase activity and both apoptotic and necrotic induction in brain tissues had been recorded at the end of the induction phase. All these alterations have been partially/fully compensated by the administration of ADMSCs, which proved their ability to penetrate the blood-brain barrier and home in the brain tissues. The molecular mechanism underlying the therapeutic effect of ADMSCs seems to be correlated with the reduction of neurodegeneration by upregulating the anti-apoptotic marker (Bcl2) and downregulating the pro-apoptotic markers (p53 and Bax) and necrotic factor (Tnfa) simultaneously.

Highlights

Alzheimer's disease (AD) is the most common form of age-related dementia affecting more than 44 million individuals around the world and this number is expected to show an increase to more than 135 million individuals around the world by 2050 (Alzheimer’s Association 2009; Albanese et al, 2014).AD is characterized by progressive memory loss which in return affects cognitive abilities, and this is associated with neural death
This was clear from the signs of dementia, open field behavioral tests especially rearing, grooming, and freezing accompanied by loss of appetite and reduction in body weight
These signs were supported at the physiological level as manifested by an increase in Acetyl Cholinesterase (AChE) activity, gradual accumulation of βamyloid, increase in oxidative stress marker (MDA) and decrease in the antioxidant defense system

Summary

Introduction

AD is characterized by progressive memory loss which in return affects cognitive abilities, and this is associated with neural death (kim et al, 2012). More recent research has pivoted focus to cytokine-mediated neuroinflammation as a major contributor to the development of AD, and among the cytokines involved in neuroinflammation, tumor necrosis factor α (TNF-α) is the most studied cytokine. Evidence suggests that inflammation promotes pathological processes that lead to AD (Akiyama et al, 2000; Tarkowski et al, 2003; McCaulley et al, 2015), where many factors and signaling pathways activated by inflammation are involved in the regulation of cell apoptosis (Yang et al, 2015). Aβ plaque formation induces neuronal apoptosis and contributes to the pathophysiology of AD (Simon et al, 2011).

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