A dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke in middle aged male and female mice

Abstract

AbstractBackgroundNutrition is a modifiable risk factor for ischemic stroke. As people age their ability to absorb some nutrients decreases, a primary example is vitamin B12. Older individuals with a vitamin B12 deficiency are at a higher risk for ischemic stroke and have worse outcome after stroke. However the mechanisms through which these occur remain unknown.ObjectiveThe aim of the study was to investigate the role of vitamin B12 deficiency in ischemic stroke outcome and mechanistic changes in a mouse model.MethodsAt 10-weeks of age male and female mice were put on control or vitamin B12 deficient diets for 4-weeks prior to and after ischemic stroke to the sensorimotor cortex. At 18 weeks of age, we assessed motor outcome using the accelerating rotarod and forepaw placement tasks. At the end of experiments, tissues were collected to assess potential mechanisms.ResultsAll animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. After ischemic stroke, male and female mice maintained on a vitamin B12 deficient diet had impaired motor function compared to control animals. In ischemic brain tissue no difference between groups in lesion volume. However, there was an increase in total apoptosis within the ischemic region of brain tissue in male vitamin B12 deficient animals. More neuronal survival was present in ischemic brain tissue of the vitamin B12 deficient group compared to controls. Additionally, there were changes in choline metabolites in ischemic brain tissue because of a vitamin B12 deficiency.ConclusionsThe data presented in this study confirms that a vitamin B12 deficiency impacts motor function in older adult male and female mice after ischemic stroke. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.Supplementary data submittedNone