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Nicotinamide: A Key Player in the Developmental Origins of Parkinson's Disease?

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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.

Conference Name not found
Acceptance Date Apr 5, 2016
Publication Date Apr 5, 2016
Publicly Available Date Mar 28, 2024
Publisher URL https://n.neurology.org/content/86/16_Supplement/I1.001

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