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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

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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.

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Authors and Affiliations

  1. Neuroscience Lab, Department of Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sara Saeidikhoo, Samira Ezi, Aysan Khatmi, Fakhroddin Aghajanpour, Reza Soltani, Mohammad Amin Abdollahifar, Ali Jahanian & Abbas Aliaghaei

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  1. Sara Saeidikhoo
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Correspondence to Sara Saeidikhoo or Abbas Aliaghaei.

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All of the following procedures were approved by the Animal Care Committee of Shahid Beheshti University of Medical Sciences. In this article, no experiment was performed by any of the authors on human participants.

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Saeidikhoo, S., Ezi, S., Khatmi, A. et al. 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. J Mol Neurosci 70, 1153–1163 (2020). https://doi.org/10.1007/s12031-020-01522-x

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