| First Author | Jadavji NM | Year | 2018 |
| Journal | Exp Neurol | Volume | 309 |
| Pages | 14-22 | PubMed ID | 30055159 |
| Mgi Jnum | J:268395 | Mgi Id | MGI:6271327 |
| Doi | 10.1016/j.expneurol.2018.07.014 | Citation | Jadavji NM, et al. (2018) A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke. Exp Neurol 309:14-22 |
| abstractText | Stroke is a leading cause of disability and death world-wide and nutrition is a modifiable risk factor for stroke. Metheylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of folic acid, a B-vitamin. In humans, a polymorphism in MTHFR (677C-->T) is linked to increased risk of stroke, but the mechanisms remain unknown. The Mthfr(+/-) mice mimic a phenotype described in humans at bp677. Using this mouse model, the aim of this study was to investigate the impact of MTHFR deficiency on stroke outcome. Male Mthfr(+/-) and wildtype littermate control mice were aged (~1.5-year-old) and trained on the single pellet reaching task. After which the sensorimotor cortex was then damaged using photothrombosis (PT), a model for ischemic stroke. Post-operatively, animals were tested for skilled motor function, and brain tissue was processed to assess cell death. Mthfr(+/-) mice were impaired in skilled reaching 2-weeks after stroke but showed some recovery at 5-weeks compared to wild types after PT damage. Within the ischemic brain, there was increased expression of active caspase-3 and reduced levels of phospho-AKT in neurons of Mthfr(+/-) mice. Recent data suggests that astrocytes may play a significant role after damage, the impact of MTHFR and ischemic investigated the impact of MTHFR-deficiency on astrocyte function. MTHFR-deficient primary astrocytes showed reduced cell viability after exposure to hypoxia compared to controls. Increased immunofluorescence staining of active caspase-3 and hypoxia-inducible factor 1-alpha were also observed. The data suggest that MTHFR deficiency decreases recovery after stroke by reducing neuronal and astrocyte viability. |
