Vitamin B12-folic acid supplementation improves memory by altering mitochondrial dynamics, dendritic arborization, and neurodegeneration in old and amnesic male mice

Abstract

Memory impairment during aging and amnesia is attributed to compromised mitochondrial dynamics and mitophagy and other mitochondrial quality control mechanisms. Mitochondrial dynamics involves the continuous process of fission and fusion of mitochondria within a cell and is a fundamental mechanism for regulating mitochondrial quality and function. An extensive range of potential nutritional supplements has been shown to improve mitochondrial health, synaptic plasticity, and cognitive functions. Previous findings revealed that supplementation of vitamin B₁₂-folic acid reduces locomotor deficits and mitochondrial abnormalities but enhances mitochondrial and neuronal health. The present study aims to explore the impact of combined vitamin B₁₂-folic acid supplementation on mitochondrial dynamics, neuronal health, and memory decline in old age and scopolamine-induced amnesia, which remains elusive. The results demonstrated that supplementation led to a noteworthy increase in recognition and spatial memory and expression of memory-related protein BDNF in old and amnesic mice. Moreover, the decrease in the fragmented mitochondrial number was validated by the downregulation of mitochondrial fission p-Drp1 (S616) protein and the increase in elongated mitochondria by the upregulation of mitochondrial fusion Mfn2 protein. The increased spine density and dendritic arborization in old and amnesic mice upon supplementation were confirmed by the enhanced expression level of PSD95 and synaptophysin. Furthermore, supplementation reduced ROS production, inhibited Caspase-3 activation, mitigated neurodegeneration, and enhanced mitochondrial membrane potential, ATP production, Vdac1 expression, myelination, in old and amnesic mice. Collectively, our findings imply that combined supplementation of vitamin B₁₂-folic acid improves mitochondrial dynamics and neuronal health, and leads to recovery of memory during old age and amnesia.

Keywords: Aging; Amnesia; Memory; Mitochondrial dynamics; Neurodegeneration; Nutritional supplement.