Hdl Handle:
http://hdl.handle.net/10034/614086
Title:
The influence of nicotinamide on the development of neurons
Authors:
Griffin, Sile; Pickard, Mark R.; Orme, Rowan; Hawkins, Clive; Williams, Adrian; Chari, Divya M.; Fricker, Rosemary
Abstract:
A major challenge in translating the promise of stem cell therapies to treat a myriad of neurodegenerative disorders is to rapidly and efficiently direct pluripotent stem cells to generate differentiated neurons. The application of active vitamin metabolites known to function in embryonic development and maintenance in the adult brain such as retinoic acid (vitamin A), ascorbic acid (vitamin C) and calcitriol (vitamin D3) have proven effective in current in-vitro differentiation protocols. Therefore, in this study we investigated whether the biologically active vitamin B3 metabolite, nicotinamide could enhance the differentiation of mouse embryonic stem cells, cultured as monolayers, into mature neurons at either early or late stages of development. Interestingly, nicotinamide elicited a dose-responsive increase in the percentage of neurons when added at an early developmental stage to the cells undergoing differentiation (days 0–7). Nicotinamide (10 mM) increased the proportion of β-III tubulin positive neurons by two fold and concomitantly decreased the total number of cells in culture, measured by quantification of 4′, 6-diamidino-2-phenylindole positive cells. This effect could result from induction of cell-cycle exit and/or selective cell death in non-neural populations. Higher levels of nicotinamide (20 mM) induced cytoxicity and cell death. This study supports previous evidence that vitamins and their metabolites can efficiently direct stem cells into neurons. Current work is focusing on the effect of nicotinamide on the process of neural induction and whether nicotinamide influences the generation of particular neuronal subtypes implicated in neurodegenerative diseases, specifically focusing on midbrain dopamine neurons; towards a therapy for Parkinson's disease.
Affiliation:
Keele University, University Hospital of North Staffordshire NHS Trust, University of Birmingham, United Kingdom
Citation:
Griffin, S., Pickard, M., Orme, R., Hawkins, C., Williams, A., Chari, D., & Fricker, R. (2014). The influence of nicotinamide on the development of neurons. Journal of Neurology, Neurosurgery and Psychiatry, 85(e4), no. 199
Journal:
Journal of Neurology, Neurosurgery and Psychiatry
Publication Date:
Oct-2014
URI:
http://hdl.handle.net/10034/614086
DOI:
10.1136/jnnp-2014-309236.199
Additional Links:
http://jnnp.bmj.com/content/85/10/e4.111.abstract
Type:
Meetings and Proceedings
Language:
en
Description:
This document is the Accepted Manuscript version of a published work that appeared in final form in Journal of Neurology, Neurosurgery and Psychiatry. To access the final edited and published work see http://dx.doi.org/10.1136/jnnp-2014-309236.199
ISSN:
0022-3050
EISSN:
1468-330X
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorGriffin, Sileen
dc.contributor.authorPickard, Mark R.en
dc.contributor.authorOrme, Rowanen
dc.contributor.authorHawkins, Cliveen
dc.contributor.authorWilliams, Adrianen
dc.contributor.authorChari, Divya M.en
dc.contributor.authorFricker, Rosemaryen
dc.date.accessioned2016-06-22T14:46:07Zen
dc.date.available2016-06-22T14:46:07Zen
dc.date.issued2014-10en
dc.identifier.citationGriffin, S., Pickard, M., Orme, R., Hawkins, C., Williams, A., Chari, D., & Fricker, R. (2014). The influence of nicotinamide on the development of neurons. Journal of Neurology, Neurosurgery and Psychiatry, 85(e4), no. 199en
dc.identifier.issn0022-3050en
dc.identifier.doi10.1136/jnnp-2014-309236.199en
dc.identifier.urihttp://hdl.handle.net/10034/614086en
dc.descriptionThis document is the Accepted Manuscript version of a published work that appeared in final form in Journal of Neurology, Neurosurgery and Psychiatry. To access the final edited and published work see http://dx.doi.org/10.1136/jnnp-2014-309236.199en
dc.description.abstractA major challenge in translating the promise of stem cell therapies to treat a myriad of neurodegenerative disorders is to rapidly and efficiently direct pluripotent stem cells to generate differentiated neurons. The application of active vitamin metabolites known to function in embryonic development and maintenance in the adult brain such as retinoic acid (vitamin A), ascorbic acid (vitamin C) and calcitriol (vitamin D3) have proven effective in current in-vitro differentiation protocols. Therefore, in this study we investigated whether the biologically active vitamin B3 metabolite, nicotinamide could enhance the differentiation of mouse embryonic stem cells, cultured as monolayers, into mature neurons at either early or late stages of development. Interestingly, nicotinamide elicited a dose-responsive increase in the percentage of neurons when added at an early developmental stage to the cells undergoing differentiation (days 0–7). Nicotinamide (10 mM) increased the proportion of β-III tubulin positive neurons by two fold and concomitantly decreased the total number of cells in culture, measured by quantification of 4′, 6-diamidino-2-phenylindole positive cells. This effect could result from induction of cell-cycle exit and/or selective cell death in non-neural populations. Higher levels of nicotinamide (20 mM) induced cytoxicity and cell death. This study supports previous evidence that vitamins and their metabolites can efficiently direct stem cells into neurons. Current work is focusing on the effect of nicotinamide on the process of neural induction and whether nicotinamide influences the generation of particular neuronal subtypes implicated in neurodegenerative diseases, specifically focusing on midbrain dopamine neurons; towards a therapy for Parkinson's disease.en
dc.language.isoenen
dc.relation.urlhttp://jnnp.bmj.com/content/85/10/e4.111.abstracten
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectNicotinamideen
dc.subjectembryonic stem cellsen
dc.subjectNeuronsen
dc.subjectParkinson's diseaseen
dc.titleThe influence of nicotinamide on the development of neuronsen
dc.typeMeetings and Proceedingsen
dc.identifier.eissn1468-330Xen
dc.contributor.departmentKeele University, University Hospital of North Staffordshire NHS Trust, University of Birmingham, United Kingdomen
dc.identifier.journalJournal of Neurology, Neurosurgery and Psychiatryen
dc.date.accepted2014-07-01en
or.grant.openaccessYesen
rioxxterms.funderUnfundeden
rioxxterms.identifier.projectUnfundeden
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2014-10en
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