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One-carbon metabolism supplementation improves outcome after stroke in aged male MTHFR-deficient mice
- Source :
- Neurobiology of Disease, Vol 132, Iss, Pp-(2019)
- Publication Year :
- 2019
-
Abstract
- The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases with age. Nutrition is a modifiable risk factor for stroke, which is a leading cause of death and disability in world-wide. Deficiencies in one‑carbon metabolism, including in methyltetrahydrofolate reductase (MTHFR), have been linked to increased risk of stroke. The Mthfr+/− mice mouse model mimic the phenotype of the MTHFR677C➔T polymorphism, such as elevated levels of homocystine. Using this mouse model, the aim of this study was to investigate the impact of dietary supplementation with 5-methylTHF, vitamin B12, and choline after ischemic stroke. Male Mthfr+/− and wildtype littermate control mice were aged (~1.5-year-old) and were placed on control diet (CD) 4-weeks prior to sensorimotor cortex damage using photothrombosis (PT), a model for ischemic stroke. Post-operatively, one group of Mthfr+/− and wildtype littermate mice were placed on 5-methylTHF, vitamin B12, and choline supplemented diet (SD). Four weeks after PT and SD motor function was assessed using the accelerating rotarod, forepaw asymmetry, and ladder beam walking tasks. Total homocysteine and cysteine levels were measured in blood. Brain tissue was processed to assess lesion volume and investigate biochemical and molecular changes. After PT and SD, Mthfr+/− mice were able to stay on the accelerating rotarod longer and used their impaired forepaw to explore more when compared to CD animals. Furthermore, total homocysteine levels in plasma and lesion volume were reduced in Mthfr+/+ and Mthfr+/− SD mice. Within the damage site, there were reduced levels of apoptotic cell death and increased neuroprotective cellular response in the brains of SD treated Mthfr+/− mice. This study reveals a critical role for one‑carbon supplementation, with 5-methylTHF, vitamin B12, and choline, in supporting improvement after ischemic stroke damage.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Aging
Homocysteine
Supplementation
Neuroprotection
lcsh:RC321-571
Choline
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Internal medicine
medicine
Animals
Vitamin B12
Neurodegeneration
Risk factor
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Stroke
Methylenetetrahydrofolate Reductase (NADPH2)
Tetrahydrofolates
Cause of death
biology
business.industry
Methylenetetrahydrofolate reductase
Brain
Recovery of Function
Cerebral ischemia
medicine.disease
digestive system diseases
3. Good health
Mice, Inbred C57BL
Sensorimotor cortex
Vitamin B 12
030104 developmental biology
Endocrinology
Neurology
chemistry
Dietary Supplements
biology.protein
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1095953X
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Neurobiology of disease
- Accession number :
- edsair.doi.dedup.....dad8c166519a57d0e943716b82f4f1ec