RESUMEN
Cell replacement therapy (CRT) is one of the most effective approaches used to alleviate symptoms of neurodegenerative syndromes such as cerebellar ataxia (CA). Human olfactory epithelium mesenchymal stem cells (OE-MSCs) have been recognized as a promising candidate for CRT, due to their distinctive features including immunomodulatory properties and ease of accessible compared to other types of MSCs. Hence, the main goal of our study was to explore the impacts of OE-MSCs transplantation on behavioral, structural, and histological deficiencies in a rat model of CA. After obtained an informed consent from volunteers, OE-MSCs were obtained from their nasal cavity. Then, OE-MSCs were characterized by the positive expression of CD73, CD90, and CD105 as MSCs as well as nestin and vimentin as primitive neuroectodermal stem cells markers. Then, the animals were randomized into three control, 3-acetylpyridine (3-AP) treated, and 3-AP + cell groups. In both experimental groups, the rats received intraperitoneal injection of 3-AP (75 mg/kg), followed by the implantation of OE-MSCs into the cerebellum of 3-AP + cell group. The impact of engrafted OE-MSCs on motor coordination and performance along with biochemical, immunohistochemical, and stereological changes in the cerebellum of the rat models of CA were investigated. According to our findings, the administration of 3-AP decreased the cerebellar GSH concentration. The injection of 3-AP also altered the morphological characteristics of the cerebellar Golgi cells. On the other hand, OE-MSCs transplantation improved motor coordination in CA. Besides, the implantation of OE-MSCs reduced caspase-3 expression and microglia proliferation in the cerebellum upon 3-AP administration. Finally, the transplant of OE-MSCs protected Purkinje cells against 3-AP toxicity. In sum, the present study revealed considerable advantages of OE-MSCs in managing CA animal model.
Asunto(s)
Ataxia Cerebelosa , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Humanos , Ratas , Ataxia Cerebelosa/terapia , Células Madre Mesenquimatosas/metabolismo , Mucosa OlfatoriaRESUMEN
Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects.