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

Nutrition 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 stroke outcome. However, the mechanisms through which these occur remain unknown. The aim of the study was to investigate the role of vitamin B12 deficiency in ischemic stroke outcome and mechanistic changes in a mouse model. Ten-month-old 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. Motor function was measured, and tissues were collected to assess potential mechanisms. All deficient mice had increased levels of total homocysteine in plasma and liver tissues. After ischemic stroke, deficient mice had impaired motor function compared to control mice. There was no difference between groups in ischemic damage volume. However, within the ischemic damage region, there was an increase in total apoptosis of male deficient mice compared to controls. Furthermore, there was an increase in neuronal survival in ischemic brain tissue of the vitamin B12 deficient mice compared to controls. Additionally, there were changes in choline metabolites in ischemic brain tissue because of a vitamin B12 deficiency. The data presented in this study confirms that a vitamin B12 deficiency worsens stroke outcome in male and female mice. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.

GRAPHICAL ABSTRACT

KEYWORDS:

• Apoptosis
• ischemic stroke
• motor function
• one-carbon metabolites
• sex differences
• vitamin B12 deficiency
• mice
• neuron‌

Acknowledgements

The authors would like to acknowledge Chelsea Adamson for her assistance in photothrombosis surgeries.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that supports the findings of this study are available in the supplementary material of this article.

Additional information

Funding

This work was supported by the Midwestern University.

Notes on contributors

Gyllian B. Yahn MBS

Gyllian B. Yahn MBS is a Doctor of Dental Medicine student at Midwestern University. Gyllian graduated undergrad with a degree in Biology and Neuroscience and completed her Masters of Biomedical Science.

Brandi Wasek

Brandi Wasek is a Research Assistant at Baylor Scott & White Health.

Teodoro Bottiglieri

Teodoro Bottiglieri, PhD, is the Program Director at the Center of Metabolomics at Baylor Scott and White Health.

Olga Malysheva

Olga Malysheva, MSc, is a Research Support Specialist in the Division of Nutritional Sciences at Cornell University.

Marie A. Caudill

Marie A. Caudill, PhD, is a Professor in the Division of Nutritional Sciences at Cornell University.

Nafisa M. Jadavji

Nafisa M. Jadavji, PhD, is an Assistant Professor in Biomedical Sciences at Midwestern University (US) and Research Assistant Professor in Neuroscience at Carleton University (Canada).