Role of altered vitamin B12 metabolism on the central nervous system homeostasis

Vitamin B12 (VitB12) and its direct role in the central nervous system (CNS) homeostasis is well-known; however, the detailed mechanisms are not clearly understood. To identify the possible basic mechanisms, regarding the CNS, involved in the alteration of the gene expression associated with VitB12 metabolism, a comparative RNA dataset analysis was performed. For this analysis, open-source databases were queried for RNA sequencing and microarray datasets generated from CNS tissues or cells under VitB12 deficiency mimicking conditions; and two datasets from mouse and one from rat models were selected. Despite the great diversity in the experimental models employed for the analysis, the comparison of these datasets highlighted a common alteration in the ribosomal gene expression under VitB12 deficiency mimicking conditions thereby indicating a possible basic and conserved response to VitB12 deficiency. Moreover, our analysis identified E2F1, a transcription factor, as a potential player in the aforementioned process. To further investigate this hypothesis, we used an in vitro model of differentiated SH-SY5Y human neuroblastoma cell line (exhibiting a neuron-like phenotype), followed by evaluating the roles of both the deficiency and excess of VitB12 on the modulation of E2F1 and its possible association with some mature neuronal markers. This possible link of E2F1 with the neuronal markers can lead to the identification of E2F1 as a potential target for maintaining CNS homeostasis under VitB12 deficiency and lay the foundation for future medical interventions.