Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer's disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β
Background: Neurodegenerative diseases (NDD) are distinguished by impairment and depletion of nerve cells; one of the most common NDDs is Alzheimer's Disease (AD), which can appear in early onset or late onset. In recent years, the secretome or conditioned medium of mesenchymal stem cells...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Tripoli University
2025-01-01
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| Series: | Open Veterinary Journal |
| Subjects: | |
| Online Access: | http://www.ejmanager.com/fulltextpdf.php?mno=213898 |
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| Summary: | Background:
Neurodegenerative diseases (NDD) are distinguished by impairment and depletion of nerve cells; one of the most common NDDs is Alzheimer's Disease (AD), which can appear in early onset or late onset. In recent years, the secretome or conditioned medium of mesenchymal stem cells provides new hope for improving conditions and preventing AD. One of the secretomes is bovine umbilical mesenchymal stem cells conditioned medium (BUMSC-CM), where BUMSC is predicted to promote neuronal proliferation potentially.
Aim:
This study analyzes the therapeutic efficiency of conditioned medium or secretome produced from BUMSC-CM in treating neurodegeneration in animal models of AD.
Methods:
Five groups consisting of twenty-five male rats were assigned: untreated (Group A, n=5), positive control group given normal saline 1 ml/100 g BW (Group B, n=5), AD rats model followed by Donepezil treatment (Group C, n=5), AD rats model with BUMSC-CM 0.2 ml/kg BW post-TMT induction (Group D, n=5), and AD rats model with BUMSC-CM 0.5 ml/kg BW post-TMT induction (Group E, n=5). Brain samples were analyzed for neuronal density using cresyl violet staining. The expression and activity of BDNF were analyzed by ELISA, in addition IL-1β, TNF-α, and NGF were analyzed by qPCR. Interactions between the main substances of BUMSC-CM and beta-amyloid protein were visualized using in silico molecular docking.
Results:
Our result demonstrated that BUMSC-CM with the dosage of 0,5 ml/kg BW significantly increased BDNF concentration. We also found that BUMSC-CM with dosage 0.2 ml/kg BW and 0.5 ml/kg BW down-regulated IL-1β and TNF-α and upregulated NGF expression. Additionally, the number of neurons in AD rats post-treated with BUMSC-CM was significantly increasing. Furthermore, the amino acids in BUMSC-CM, including isoleucine, leucine, and valine, bind to amyloid beta protein via interactions that are hydrophobic and hydrogen-bonded.
Conclusion:
In this study, the neuroprotective potential of BUMSC-CM was demonstrated by its ability to upregulate BDNF and NGF while downregulating IL-1β and TNF-α. Additionally, BUMSC-CM showed potential to promote neuron proliferation in the hippocampus regions of a rat AD model. The main constituents in BUMSC-CM adhere to amyloid beta protein, hence diminishing the likelihood of neurodegenerative disorders, specifically AD. [Open Vet J 2025; 15(1.000): 151-161] |
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| ISSN: | 2226-4485 2218-6050 |