Riboflavin (Vitamin B2) Accumulation Modulates Neuronal Cellular Homeostasis in Typical Brain Development and Cerebral Palsy

Abstract

The developing brain requires high energy demands and metabolic efforts to regulate oxidative stress and myelination. Early insults cause mitochondrial dysfunction and compromise these pathways, potentially leading to cerebral palsy (CP), a severe and incurable neurological disorder that begins in childhood. Through a rodent preclinical study, we demonstrated that vitamin B2 (riboflavin), administered at a high dose (100 mg/kg), is accumulated in healthy (B2C) or paralytic (B2CP) brains and participates in neurodevelopment. Redox homeostasis was maintained in B2C through decreased malondialdehyde and carbonyls and increased glutathione-S-transferase activity. In B2CP rodents, there was a reduction in carbonyls and increased superoxide dismutase activity. Mitochondrial morphometric analysis suggests that riboflavin treatment increases biogenesis in controls and reduces mitochondrial deformation in CP. Ultrastructural analysis revealed increased myelin sheath thickness in B2C. Additionally, myelin figure formation and mitochondrial and axonal disintegration in CP were reduced by B2. Our evidence supports vitamin B2 accumulation as a beneficial mechanism to support energy homeostasis and mitochondrial demands that occur during typical neurodevelopment or in the face of CP.