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Sertoli Cells Avert Neuroinflammation-Induced Cell Death and Improve Motor Function and Striatal Atrophy in Rat Model of Huntington Disease

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Abstract

Huntington’s disease (HD) is a genetically heritable disorder, linked with continuing cell loss and degeneration mostly in the striatum. Currently, cell therapy approaches in HD have essentially been focused on replenishing or shielding cells lost over the period of the disease. Herein, we sought to explore the in vitro and in vivo efficacy of primary rat Sertoli cells (SCs) and their paracrine effect against oxidative stress with emphasis on HD. Initially, SCs were isolated and immunophenotypically characterized by positive expression of GATA4. Besides, synthesis of neurotrophic factors of glial cell-derived neurotrophic factor and VEGF by SCs were proved. Next, PC12 cells were exposed to hydrogen peroxide in the presence of conditioned media (CM) collected from SC (SC-CM) and cell viability and neuritogenesis were determined. Bilateral striatal implantation of SC in 3-nitropropionic acid (3-NP)-lesioned rat models was performed, and 1 month later, post-graft analysis was done. According to our in vitro results, the CM of SC protected PC12 cells against oxidative stress and remarkably augmented cell viability and neurite outgrowth. Moreover, grafted SCs survived, exhibited decreases in both gliosis and inflammatory cytokine levels, and ameliorated motor coordination and muscle activity, together with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. In conclusion, our results indicate that SCs provide a supportive environment, with potential therapeutic benefits aimed at HD.

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Acknowledgements

This project is part of the M.S.C thesis of H. Ahmadi.

Funding

This study was funded by the Vice Chancellor of Research of the Shahid Beheshti University of Medical Sciences (grant number 11621).

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Authors and Affiliations

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

    Houssein Ahmadi, Yousef Sadeghi, Mohammad Amin Abdollahifar & Abbas Aliaghaei

  2. Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Mahdi Eskandarian Boroujeni

  3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fariba Khodagholi

  4. Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Gholam Houssein Meftahi & Mohammadmehdi Hadipour

  5. Department of Neuroscience, Saveh University of Medical Sciences, Saveh, Iran

    Amir-Hossein Bayat

  6. Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, 32611, USA

    Fatemeh Shaerzadeh

Authors
  1. Houssein Ahmadi
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  2. Mahdi Eskandarian Boroujeni
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  3. Yousef Sadeghi
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  4. Mohammad Amin Abdollahifar
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  5. Fariba Khodagholi
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  6. Gholam Houssein Meftahi
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  7. Mohammadmehdi Hadipour
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  8. Amir-Hossein Bayat
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  9. Fatemeh Shaerzadeh
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  10. Abbas Aliaghaei
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Corresponding author

Correspondence to Abbas Aliaghaei.

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Conflict of Interest

The authors declare that they have no competing interests.

Ethical Approval

All procedures performed in this study involving animals were in accordance with the ethical standards of the ethics committee of Shahid Beheshti University of Medical Sciences and under approval no. IR.SBMU.MSP.REC.1396.604.

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Ahmadi, H., Boroujeni, M.E., Sadeghi, Y. et al. Sertoli Cells Avert Neuroinflammation-Induced Cell Death and Improve Motor Function and Striatal Atrophy in Rat Model of Huntington Disease. J Mol Neurosci 65, 17–27 (2018). https://doi.org/10.1007/s12031-018-1062-x

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  • DOI: https://doi.org/10.1007/s12031-018-1062-x

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