Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Medical Biochemistry

Parkinson{u2019}s disease is a neurodegenerative disease that leads to loss of dopaminergic neurons in the substantia nigra of the midbrain, as well as alpha-synuclein protein accumulation. Levodopa combined with carbidopa is the standard treatment. Mesenchymal stem cell (MSC) derived extracellular vesicles (exosomes) are now widely tested for their regenerative and therapeutic effects in many diseases. We aimed to investigate the role of ciRS-7 in treatment of Parkinson{u2019}s disease by MSC-derived EVs (exosomes). Methods: The experiment was done on thirty-two white albino rats grouped as follows, group (1): eight healthy rats as normal control, group (2) eight experimentally induced Parkinson{u2019}s disease rats, group (3): eight experimentally induced Parkinson{u2019}s disease rats received levodopa/carbidopa orally, and group (4): eight experimentally induced Parkinson{u2019}s disease rats received MSC derived EVs (exosomes) intranasally. Brain tissue alpha-synuclein was assessed by ELISA. Quantitative RT-PCR was done to assess regeneration of midbrain tissue by measuring miR-7 and ciRS-7 gene expression. Additionally, histopathological and immune-histochemical examinations were done to confirm dopaminergic neuron regeneration. Results: In the treated groups either with EVs (exosomes) or levodopa/carbidopa, regenerative results were achieved but were more significant in EVs (exosomes) treated group. There was a significant decrease in brain tissue alpha-synuclein in levodopa/carbidopa and EVs (exosomes) treated groups compared to Parkinson{u2019}s disease group (p value =0.006 and <0.0001 respectively). Regarding the assessed genes (ciRS-7 and miR-7) there was a significant decrease in gene expression of ciRS-7 in the levodopa/carbidopa treated group compared to Parkinson{u2019}s disease group (p value<0.0001) and in the EVs (exosomes) treated group compared to Parkinson{u2019}s disease and levodopa/carbidopa treated groups (p value<0.0003 and p value = 0.046 respectively)

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