Effect of Sertoli Cell Transplantation on Reducing Neuroinflammation-Induced Necroptosis and Improving Motor Coordination in the Rat Model of Cerebellar Ataxia Induced by 3-Acetylpyridine

• Published in: Journal of molecular neuroscience 2020-07, Vol.70 (7), p.1153-1163
• Main Authors: Saeidikhoo, Sara, Ezi, Samira, Khatmi, Aysan, Aghajanpour, Fakhroddin, Soltani, Reza, Abdollahifar, Mohammad Amin, Jahanian, Ali, Aliaghaei, Abbas
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Ataxia; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell survival; Cell viability; Cells, Cultured; Cerebellar ataxia; Cerebellar Ataxia - etiology; Cerebellar Ataxia - therapy; Cerebellum; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Hydrogen peroxide; Immunohistochemistry; In vivo methods and tests; Inflammation; Male; Movement; Necroptosis; Neurochemistry; Neurology; Neuronal-glial interactions; Neuroprotection; Neurosciences; Neurotrophic factors; PC12 Cells; Pheochromocytoma cells; Proteomics; Pyridines - toxicity; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sertoli cells; Sertoli Cells - metabolism; Sertoli Cells - transplantation; Signs and symptoms; Stem Cell Transplantation - methods; Surgical implants; Transplantation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vimentin; Vimentin - genetics; Vimentin - metabolism
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01522-x

To date, no certain cure has been found for patients with degenerative cerebellar disease. In this trial, we examined the in vivo and in vitro neuroprotective effects of Sertoli cells (SCs) on alleviating the symptoms of cerebellar ataxia. Testicular cells from an immature male rat were isolated and characterized by immunocytochemical analysis for somatic cell markers (anti-Mullerian hormone, vimentin). The protein assessment had already confirmed the expression of neurotrophic factors of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial factor (VEGF). In vitro neuroprotective impact of SCs was determined after exposing PC12 cells to Sertoli cell–conditioned media (SC-CM) and H 2 O 2 , simultaneously. Afterwards, ataxia rat models were induced by a single dose of 3-AP (3-acetylpyridin), and 3 days later, SCs were bilaterally implanted. Motor and neuromuscular activity test were conducted following SC transplantation. Finally, immunohistochemistry against RIPK3 and Iba-1 was done in our generation. The in vivo results revealed substantial improvement in neuromuscular response, while ataxia group exhibited aggravated condition over a 28-day period. Our results suggested enhanced motor function and behavioral characteristics due to the ability of SCs to suppress necroptosis and consequently extend cell survival. Nevertheless, more studies are required to affirm the therapeutic impacts of SC transplantation in human cerebellar ataxia. In vitro data indicated cell viability was increased as a result of SC-CM with a significant reduction in ROS.