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.

Abstract

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 H2O2, 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.

• Authors: Sara Saeidikhoo, Samira Ezi, Aysan Khatmi, Fakhroddin Aghajanpour, Reza Soltani, Mohammad Amin Abdollahifar, Ali Jahanian, Abbas Aliaghaei
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 70 Issue 7 Pg. 1153-1163 (Jul 2020) ISSN: 1559-1166 [Electronic] United States
• PMID: 32166479 (Publication Type: Journal Article)

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• Pyridines
• Vascular Endothelial Growth Factor A
• Vimentin
• 3-acetylpyridine

Topics

• Animals
• Cells, Cultured
• Cerebellar Ataxia (etiology, therapy)
• Glial Cell Line-Derived Neurotrophic Factor (genetics, metabolism)
• Male
• Movement
• Necroptosis
• PC12 Cells
• Pyridines (toxicity)
• Rats
• Rats, Sprague-Dawley
• Rats, Wistar
• Sertoli Cells (metabolism, transplantation)
• Stem Cell Transplantation (methods)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vimentin (genetics, metabolism)