Pjetri Eneda, Zeisel Steven H
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, United States.
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, United States; Department of Nutrition, Gillings Global School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States.
Behav Brain Res. 2017 Aug 14;332:71-74. doi: 10.1016/j.bbr.2017.05.051. Epub 2017 May 27.
The MTHFD1 gene encodes for methylenetetrahydrofolate dehydrogenase 1, an enzyme that has an important role in folate-mediated one-carbon metabolism. In people, a single nucleotide polymorphism of this gene (1958G>A; rs2236225) is associated with increased risk for bipolar disorder and schizophrenia, neural tube and other birth defects. Mice homozygous for a loss of Mthfd1 via a gene-trap mutation are not viable, and heterozygotes, though they appear healthy, have metabolic imbalances in the folate- and choline-mediated 1-carbon metabolic pathways. In this study, we evaluated cognitive function in Mthfd1 male and female mice using a behavioral battery composed of eight different tests. We found that these mice display impaired cue-conditioned learning, while other behaviors remain intact.
MTHFD1基因编码亚甲基四氢叶酸脱氢酶1，该酶在叶酸介导的一碳代谢中起重要作用。在人类中，该基因的一个单核苷酸多态性（1958G>A；rs2236225）与双相情感障碍、精神分裂症、神经管及其他出生缺陷的风险增加有关。通过基因陷阱突变导致Mthfd1缺失的纯合子小鼠无法存活，杂合子小鼠虽然看起来健康，但在叶酸和胆碱介导的一碳代谢途径中存在代谢失衡。在本研究中，我们使用由八项不同测试组成的行为组合评估了Mthfd1雄性和雌性小鼠的认知功能。我们发现这些小鼠表现出线索条件学习受损，而其他行为保持完好。
