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Human Adipose-Derived Stem Cells Reduce Receptor-Interacting Protein 1, Receptor-Interacting Protein 3, and Mixed Lineage Kinase Domain-Like Pseudokinase As Necroptotic Markers in Rat Model of Alzheimer's Disease Publisher Pubmed



Eftekharzadeh M1, 2 ; Simorgh S3 ; Doshmanziari M1 ; Hassanzadeh L4, 5 ; Shariatpanahi M2, 6
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine
  2. 2. Neuroscience Research Center, Iran University of Medical Sciences, Tehran, 1449614535, Iran
  3. 3. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Nuclear Medicine, School of Medicine, Rajaie Cardiovascular, Medical and Research Center
  5. 5. Department of Medicinal Chemistry, School of Pharmacy.International Campus, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Toxicology and Pharmacology, School of Pharmacy, International Campus, Tehran, Iran

Source: Indian Journal of Pharmacology Published:2020


Abstract

OBJECTIVES: Alzheimer's disease (AD) is a constant, developing brain impairment that is described as the aggregation of misfolded amyloid-beta-peptide (Ab) and abnormal tau protein in the brain. Stem cell therapy became a favorable candidate for the regeneration of neurodegenerative disorders like AD, but there is still shortage of knowledge about the underlying mechanisms. The goal of this survey was the determination of the necroptotic pathway as the possible mechanism for the effect of human adipose-derived stem cells (hADSCs) in the rat model of AD. MATERIALS AND METHODS: Twelve rats were consumed, dividing into four groups: Control, sham, AD model and AD + stem cell groups. We utilized Nissl and Thioflavin S staining for determining histological changes and immunofluorescent techniques for evaluating necroptotic markers in different regions of the hippocampus. RESULTS: The confirmation of AD model was approved with histological examination. The findings indicated more distinct Thio-S stain and an increased number of dead cells in AD rats comparing to other groups. Alternatively, the dead cells number in the CA3 area significantly lessened in AD + stem cell group comparing to AD group. Data showed that hADSCs significantly decreased the expression of necroptotic markers (receptor-interacting protein 1, receptor-interacting protein 3 and mixed lineage kinase domain-like pseudokinase (MLKL)) in AD + stem cell group compared to AD group in different regions of the hippocampus. CONCLUSION: Our findings revealed that the intravenous injection of hADSCs reduced necroptosis and consequently declined the death of neuronal cells in the hippocampus of AD rats. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.
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