A Dietary Vitamin B12 Deficiency Impairs Balance and Coordination After Ischemic Injury to the Sensorimotor Cortex in Adult Male and Female Mice

Abstract

ObjectivesThe majority of the world’s population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. MethodsAt 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. ResultsAll animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. ConclusionsVitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding SourcesMidwestern University Start-Up Funds.