Effects of disrupted serine hydroxymethyltransferase 1 (Shmt1) gene expression on motor function and myelin degeneration in vitamin B12 deficient mice Academic Article uri icon

abstract

  • Previous studies have shown disrupted Shmt1 enzyme activity to be associated with neurocognitive effects, impaired dTMP biosynthesis, and genomic uracil misincorporation. Moreover, misincorporation of uracil in DNA has been identified as a potential mechanism underlying the neurodegenerative effects of vitamin B12 deficiency. The aims of this study are twofold: 1) to evaluate the effects of combining vitamin B12 deficiency and impaired Shmt1expression on motor function and histological observations in the spinal cords of adult mice 2) to identify causal mechanisms underlying impaired B12 metabolism and myelin degeneration.. Experimental vitamin B12 deficient diets with different folic acid content (0 mg/kg, 2 mg/kg, 8 mg/kg diet ) were fed to adult Shmt1+/+ and Shmt1+/ mice from weaning through the duration of the study. In order to identify changes in voluntary motor control, several tests were employed to assess motor coordination and balance: accelerating rotarod, staggered speed rotarod, and the beam traversal test. The expression of myelin basic protein (MBP) was analyzed with staining in light microscopy and immunohistochemistry. We hypothesize that mice heterozygous for Shmt1 will be sensitized to vitamin B12 deficiency induced neuropathology resulting in reduced motor activity and decreased spinal cord MBP expression. The results of this study support a role for vitamin B12 deficiency in dTMP synthesis and the development of myelin degeneration in the central nervous system. The results will provide new insights into the prevention and treatment of neurodegenerative diseases.

published proceedings

  • The FASEB Journal

author list (cited authors)

  • Awuah, E., Field, M., & Stover, P.

citation count

  • 1

complete list of authors

  • Awuah, Eunice||Field, Martha||Stover, Patrick

publication date

  • April 2015

publisher