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Introduction: Aging is a normal physiological process that affects all organs in the body including the cerebellum. Metformin is an anti-diabetic drug that is used in some age-related diseases. Regenerative medicine using adipose tissue derived mesenchymal stem cells (ADMSCs) is an emerging promising strategy.
Aim: to compare between the role of ADMSCs and metformin on the age-related structural changes of the cerebellum in female albino rats.
Materials and methods: The study included 55 female rats of different ages. They were divided into three groups according to their ages: group I (Adult rats, from 4-6 months), group II (Old rats, from 12-18 months) and group III (Senile rats, from 24-28 months). group II and group III were further subdivided into three subgroups, Subgroup a: rats were left without treatment. Subgroup b: rats were given a single dose of 1X106 ADMSCs via tail vein. Subgroup c: Rats received 300mg/kg metformin/day orally. Rats were sacrificed after four weeks. The cerebella were collected and processed for H&E, toluidine blue, immuno-histochemical stains using glial fibrillary acidic protein (GFAP) and synaptophysin. Transmission electron microscopic examination and histomorphometric studies were also performed.
Results: Light and electron microscopic examination of the cerebellum of non-treated old and senile rats (subgroups IIa and IIIa) revealed age-related structural changes compared to group I. Purkinje cells showed degenerative changes with a significant decrease in their mean number. Significant decrease in the mean optical density of Nissl granules was also noticed. The granular layer showed small widely separated granule cells with an apparent decrease in their number. A significant decrease in the mean number of astrocytes in GFAP sections and the mean optical density of synaptophysin reaction was also noticed in the non-treated subgroups (IIa and IIIa) compared to adult group I. Degeneration of axons and atrophy of myelin sheath were also noticed in the medulla of non-treated rats. The structural changes were more obvious in subgroup IIIa compared to subgroup IIa. In ADMSCs treated subgroups (IIb and IIIb), significant improvement of these changes was more noticeable compared to the corresponding metformin treated subgroups (IIc and IIIc) which was confirmed by statistical analysis.
Conclusion: ADMSCs were more effective than metformin in ameliorating some age-related structural changes of the cerebellum in female albino rats.