Internationale Zeitschrift für Physikalische Medizin und Rehabilitation
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Transcriptome Changes and Neuronal Degeneration in an In Vitro Model of B Vitamin Depletion

Niels Banek, Leonie Martens, Natalie Daluege, Nikisha Carty, Sebastian Schmeier, Oltea Trutz, Kenneth W. Young*, Patrizia Bohnhorst*

Background: The neurotropic B vitamins such as thiamine (B1), pyridoxine (B6), and cobalamin (B12) play a pivotal role in the maintenance of neuronal viability and contribute essentially to a healthy nervous system. Furthermore, it is well recognised that deficiencies in neurotropic B vitamins can lead to a variety of neurological conditions and peripheral neuropathies. However, to date, the effect of B vitamin depletion on modulation of genes and cellular pathways has not been fully assessed.

Materials and Methods: In this current study we used RNA sequencing and transcriptomic analysis to investigate gene expression changes in primary cultures of mouse Dorsal Root Ganglion (mDRG) neurons in response to neurotropic B vitamin depletion. Gene Ontology (GO) enrichment analysis identified significant changes in pathways and processes associated with energy metabolism and neuronal death when comparing mDRG neurons grown in optimal conditions supplemented with vitamins B1, B6, B12 to vitamin B free medium lacking these B vitamins.

Results: In total 161 genes were differentially regulated after 3 days in vitamin B free medium. This number increased to 735 genes differentially regulated after 6 days in vitamin B free medium. We also found activation of certain prosurvival pathways, presumably as compensatory mechanisms to B vitamin depletion. A complex induction of prosurvival and pro-death pathways therefore appears to be responsible for ultimately determining the fate of neurons.

Conclusion: Taken together, our study identifies gene expression changes and the involvement of pathways potentially linked to mDRG neurodegeneration occurring in response to depletion of neurotropic B vitamins.