Related Experiment Video
Updated: Aug 7, 2026
Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
Published on: October 10, 2012
Microarray analysis of brain RNA in mice with methylenetetrahydrofolate reductase deficiency and hyperhomocysteinemia
Zhoutao Chen1, Bing Ge, Thomas J Hudson
1Department of Biology, McGill University, Montreal, Canada.
Abstract:
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which is associated with increased risk for cardiovascular disease, stroke and possibly other neurological disorders. Microarray analysis of brain RNA from day 14 Mthfr(-/-) mice revealed several genes with altered expression. Expression changes in inositol 1,4,5-triphosphate receptor, type 1 (Itpr1), proteolipid protein (Plp), neurogenic differentiation factor 1 (Neurod1), S100 calcium binding protein A8 (S100a8), and methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) were confirmed by RT-PCR. We propose that neuronal damage by hyperhomocysteinemia may involve disruption of intracellular calcium.
Insights
Methylenetetrahydrofolate reductase (MTHFR) deficiency causes high homocysteine, increasing risks for stroke and heart disease. This study found altered gene expression in MTHFR-deficient mouse brains, suggesting disrupted calcium signaling contributes to neuronal damage.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Methylenetetrahydrofolate reductase (MTHFR) deficiency is a primary genetic cause of hyperhomocysteinemia.
- Elevated homocysteine levels are linked to increased risks of cardiovascular disease, stroke, and neurological disorders.
Purpose of the Study:
- To investigate the molecular mechanisms underlying neuronal damage in MTHFR deficiency.
- To identify genes with altered expression in the brain due to MTHFR deficiency.
Main Methods:
- Microarray analysis of brain RNA from Mthfr(-/-) mice at day 14.
- Validation of gene expression changes using RT-PCR.
Main Results:
- Microarray analysis revealed significant alterations in the expression of several genes in Mthfr(-/-) mouse brains.
- Confirmed expression changes for key genes including Itpr1, Plp, Neurod1, S100a8, and Mthfd2.
- Identified altered expression of genes involved in calcium signaling and neuronal function.
Conclusions:
- Hyperhomocysteinemia resulting from MTHFR deficiency may lead to neuronal damage.
- Disruption of intracellular calcium homeostasis is a potential mechanism contributing to this neuronal damage.
