%0 Journal Article %A Gyllian B. Yahn %A Brandi Wasek %A Teodoro Bottiglieri %A Olga Malysheva %A Marie A. Caudill %A Nafisa M. Jadavji %T A dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke to the sensorimotor cortex in middle aged male and female mice %D 2021 %R 10.1101/2021.08.17.456684 %J bioRxiv %P 2021.08.17.456684 %X The 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 the proportion is projected to increase to 21% by 2050. Currently, ischemic stroke predominately affects the elderly. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, most older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin that take place during the aging process. Using a mouse model system, we investigated the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in ischemic versus non-ischemic brain tissue. At 10-weeks of age male and female C57Bl/6J mice were put on control or vitamin B12 deficient 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. Animals were continued on diets for 4 weeks after damage. At 18 weeks of age, we assessed stroke outcome using the accelerating rotarod and forepaw placement tasks. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissues to assess histological and biochemical measurements. All 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 control diet animals after ischemic stroke. In ischemic brain tissue no difference between groups in lesion volume was observed. More neuronal survival was present in ischemic brain tissue of the vitamin B12 deficient group compared to controls. There were changes in choline metabolites in ischemic brain tissue as a result of diet and sex. In conclusion, the 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.Competing Interest StatementThe authors have declared no competing interest.tHcyTotal homocysteine;NeuNneuronal nuclei;DAPI4′,6-diamidino-2-phenylindole; %U https://www.biorxiv.org/content/biorxiv/early/2021/08/18/2021.08.17.456684.full.pdf