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bioRxiv · 10.1101/2022.04.04.487028

Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency

Poole, J.·Jasbi, P.·Pascual, A.·North, S.·Kwatra, N.·Weissig, V.·Gu, H.·Bottiglieri, T.·Jadavji, N. M.
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Abstract

The global population is aging and the prevalence of age-related diseases, such as stroke, is predicted to increase. A vitamin B12 deficiency (vit. B12 def.) is common in the elderly, because of changes in metabolism. Clinical studies have reported that a vit. B12 def results in worse outcome after stroke, the mechanisms through which a vit. B12 def. changes the brain requires further investigation. This study investigated the role of vit. B12 def. on stroke outcome and mechanisms using aged female mice. Eighteen month old females were put on a control or vit. B12 def. diet for four weeks, after which an ischemic stroke was induced in the sensorimotor cortex. After damage, motor function was measured and animals were euthanized and tissues were collected for analysis. Vit. B12 def. animals had increased levels of total homocysteine in plasma and liver, choline levels were also increased in the liver. Vit. B12 def. animals had larger damage volume in brain tissue and more apoptosis. In the cecum, changes in creatinine and methylmalonic acid were observed in vit. B12 def. animals, pathway analysis showed dysfunction in B12 transport. Analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. B12 def animals. Meanwhile, pathway analysis showed significant, widespread dysfunction in phenylalanine, tyrosine, and tryptophan biosynthesis. Motor function after stroke was impaired in vit. B12 def. animals. A dietary vitamin B12 deficiency impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue.

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Poole, J., Jasbi, P., Pascual, A., North, S., Kwatra, N., Weissig, V., Gu, H., Bottiglieri, T., Jadavji, N. M.. 2022-04-05. Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency. https://doi.org/10.1101/2022.04.04.487028

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