Abstract
OBJECTIVE: To investigate the role of vitamin B3 (nicotinamide) on midbrain dopaminergic neuron development. BACKGROUND: The active forms of vitamins A & C are linked to optimal development of neurons . Little is known regarding the role of vitamin B3 even though poor cognitive development and parkinsonism were features of pellagra . DESIGN/METHODS: Monolayer mouse embryonic stem cell cultures (mESC; Sox1GFP knock-in 46C cell line) were treated with nicotinamide for different durations and immunocytochemistry/ fluorescence microscopy was performed to assess the expression of stem cell, neural progenitor (NP) and neuronal subtype markers. RESULTS: Nicotinamide accelerated the conversion process of mESCs to neurons with a catecholaminergic phenotype. Specifically, the proportion of proliferating cells was significantly reduced in nicotinamide-treated cultures - that is, nicotinamide regulates the proliferation-to-differentiation switch from NPs to neurons during development. Nicotinamide drives dopamine neuron differentiation (10mM) as effectively as known cocktails of signalling factors, and acts in a dose-dependent manner in a defined time-window - with high doses (20mM) however causing toxicity. CONCLUSIONS: Nicotinamide aids the conversion of stem cells to dopaminergic neurons increasing efficiency and safety of the cells produced, and reducing cost; important as we progress towards patient-specific cell replacement therapy for Parkinson’s . Our data also suggest that nicotinamide is a key signalling factor required in a definable dosage range at key times for the formation of a healthy population of dopamine neurons. An optimal maternal to foetal dietary dosage of nicotinamide - neither too low nor too high - could be linked to Parkinson’s disease later in life.
Disclosure: Dr. Williams has nothing to disclose. Dr. Griffin has nothing to disclose. Dr. Pickard has nothing to disclose. Dr. Fricker has nothing to disclose.
Saturday, April 16 2016, 1:00 pm-5:30 pm
- Copyright © 2016 by AAN Enterprises, Inc.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.