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Molecular Neurobiology

, Volume 51, Issue 2, pp 791–807 | Cite as

Differentiating neurons derived from human umbilical cord blood stem cells work as a test system for developmental neurotoxicity

  • Mahendra P. Kashyap
  • Vivek Kumar
  • Abhishek K. Singh
  • Vinay K. Tripathi
  • Sadaf Jahan
  • Ankita Pandey
  • Ritesh K. Srivastava
  • Vinay K. Khanna
  • Aditya B. PantEmail author
Article

Abstract

Differentiating neuronal cells derived from human umbilical cord blood stem cells have been used as an in vitro tool for the assessment of developmental neurotoxicity of monocrotophos (MCP), an organophosphate pesticide. The differentiating cells were exposed to MCP during the different stages of maturation, viz., days 2, 4, and 8, and changes in the makers of cell proliferation, neuronal differentiation, neuronal injuries, and receptors were studied. We found significant upregulation in the different MAPKs, apoptosis, and neurogenesis markers and downregulation in the cell proliferation markers during neuronal differentiation. We further identified significant upregulation in the expression of different MAPKs and proteins involved in oxidative stress, apoptosis, and calpain pathways in the mid-differentiating cells exposed to MCP. The upregulated levels of these proteins seem to be the main cause of alteration during the differentiation process towards apoptosis as a fine-tune of pro-apoptotic and anti-apoptotic proteins are desirable for the process of differentiation without apoptosis. The decreased acetylcholinesterase activity, dopaminergic, and cholinergic receptors and increased acetylcholine levels in the differentiating neuronal cells indicate the vulnerability of these cells towards MCP-induced neurotoxicity. Our data confirms that differentiating neuronal cells derived from human umbilical cord stem cells could be used as a powerful tool to assess the developmental neurotoxicity in human beings.

Keywords

Umbilical cord blood stem cells Developmental neurotoxicity Apoptosis Alternative testing strategies Monocrotophos Organophosphates 

Notes

Acknowledgments

Authors are grateful to the Director, the IITR, Lucknow, India, for his keen interest to the study. The work was supported by the Council of Scientific and Industrial Research (CSIR), New Delhi, India, [Grant No. BSC0111/INDEPTH/CSIR Network Project] and the Department of Biotechnology (DBT), New Delhi, India [Grant No. 102/IFD/SAN/PR-1524/2010-2011]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Declaration of no conflict of interest

Authors of this manuscript have no conflict of interest among them or anybody else regarding the scientific contents, financial matters, or otherwise.

Supplementary material

12035_2014_8716_MOESM1_ESM.doc (310 kb)
Figure S1 List of 96 genes studied using TaqMan low-density array (TLDA) in 384-well plate format (DOC 309 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mahendra P. Kashyap
    • 1
  • Vivek Kumar
    • 1
  • Abhishek K. Singh
    • 1
  • Vinay K. Tripathi
    • 1
  • Sadaf Jahan
    • 1
  • Ankita Pandey
    • 1
  • Ritesh K. Srivastava
    • 1
  • Vinay K. Khanna
    • 1
  • Aditya B. Pant
    • 1
    Email author
  1. 1.In Vitro Toxicology LaboratoryCSIR-Indian Institute of Toxicology ResearchLucknowIndia

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