Dottorato in BIOLOGIA CELLULARE E DELLO SVILUPPO

Titolo della tesi: An in vitro evaluation on the role of vitamin B12 in neural homeostasis

Medical evidence suggests a direct role of Vitamin B12 (VitB12) in neural homeostasis. A high dose of VitB12 is often employed for its beneficial role in the recovery of some neural impairments. Since there exists a wide disparity and knowledge gap in the literature for the different VitB12 doses employed, we developed a study to address the dose-dependent effects offered by VitB12 and their potential roles in neural homeostasis and recovery. Here, we employed an in vitro neural cell model with differentiated SH-SY5Y cells and exposed them with hydrogen peroxide (H2O2) to stimulate neural damage, followed by recovery in a physiological dose or a high dose of VitB12. The physiological dose of VitB12 offered a more efficient recovery from the H2O2 insult by enhancing the cell survival, neural elongation, mitochondrial metabolic activities and morphodynamics, and the overall lipid composition, in comparison with the high dose of VitB12. Furthermore, the enhanced recovery observed with the physiological dose may be attributed to its ability to induce antioxidant defences earlier than the high dose. Our bioinformatics analysis employed various gene expression datasets from rodents with different VitB12 metabolic defects, in order to evaluate the possible underlying mechanisms associated with VitB12 deficiency. We observed an alteration in the ribosomal gene regulation, which could be ascribed to the transcription factor E2F1. Therefore, we confirm the association between E2F1 and VitB12 in our in vitro model. This study, employing a human in vitro neural model and a bioinformatic approach, highlights the beneficial role of a physiological dose of VitB12 and identifies E2F1 as a possible target in reversing the effects due to VitB12 deficiency.