NDLI: Gestational Age and Sex Influence the Susceptibility of Human Neural Progenitor Cells to Low Levels of MeHg

Content Provider	Springer Nature Link
Author	Edoff, Karin Raciti, Marilena Moors, Michaela Sundström, Erik Ceccatelli, Sandra
Copyright Year	2017
Abstract	The developing nervous system is highly susceptible to methylmercury (MeHg), a widespread environmental neurotoxic contaminant. A wide range of morphological and functional outcomes have been described; however, there are still open questions regarding the mechanisms behind the developmental neurotoxic effects induced by low-level exposure. In the present study, we have examined the effects of nanomolar concentrations of MeHg on primary fetal human progenitor cells (hNPCs) with special focus on the role played by developmental stage and sex on the neurotoxic outcome. We found that neurospheres derived from earlier gestational time points exhibit higher susceptibility to MeHg, as they undergo apoptosis at a much lower dose (25 nM) as compared to neurospheres established from older fetuses (100 nM). At subapoptotic concentrations (10 nM), MeHg inhibited neuronal differentiation and maturation of hNPCs, as shown by a reduced number of Tuj1-positive cells and a visible reduction in neurite extension and cell migration, associated with a misregulation of Notch1 and BDNF signaling pathways. Interestingly, cells derived from male fetuses showed more severe alterations of neuronal morphology as compared to cells from females, indicating that the MeHg-induced impairment of neurite extension and cell migration is sex-dependent. Accordingly, the expression of the CDKL5 gene, a major factor regulating neurite outgrowth, was significantly more downregulated in male-derived cells. Altogether, gestational age and sex appear to be critical factors influencing in vitro hNPC sensitivity to low levels of MeHg.
Starting Page	683
Ending Page	693
Page Count	11
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	32
Issue Number	4
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2017-07-29
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Developmental neurotoxicity Methylmercury Human neural progenitor cells Cell migration Sex-related differences Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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