Cerebral vascular dysfunction in methionine synthase-deficient mice

Area of Science:

• Biochemistry
• Physiology
• Neuroscience

Background:

• Methionine synthase (MS) is crucial for remethylating homocysteine to methionine, a folate-dependent process.
• Endothelial dysfunction is linked to various cardiovascular and neurological diseases.

Purpose of the Study:

• To investigate if impaired methionine synthase (MS) function affects endothelial function in mice.
• To determine the role of folate availability in MS deficiency-induced endothelial dysfunction.

Main Methods:

• Utilized mice heterozygous for the Mtr gene (encoding MS) and wild-type littermates.
• Administered control and low-folate (LF) diets.
• Assessed cerebral arteriole dilatation to acetylcholine using microscopy.
• Quantified superoxide and hydrogen peroxide levels in cerebral arterioles.

Main Results:

• Mice with MS deficiency (Mtr(+/-)) showed blunted cerebral arteriole dilatation compared to wild-type (Mtr(+/+)) mice on a control diet.
• Both Mtr(+/+) and Mtr(+/-) mice on an LF diet exhibited impaired arteriole dilatation.
• Elevated oxidative stress markers (superoxide, hydrogen peroxide) were observed in Mtr(+/-) mice on a control diet and in both genotypes on an LF diet.

Conclusions:

• Defective homocysteine remethylation, whether due to MS deficiency or folate deficiency, causes oxidative stress.
• This oxidative stress leads to endothelial dysfunction in the mouse cerebral microcirculation.