Neural tube defects (NTDs) are serious congenital malformations. Excessive maternal homocysteine (Hcy) increases the risk of NTDs, while its mechanism remains elusive. Here we report the role of histone homocysteinylation in neural tube closure (NTC). A total of 39 histone homocysteinylation sites are identified in samples from human embryonic brain tissue using mass spectrometry. Elevated levels of histone KHcy and H3K79Hcy are detected at increased cellular Hcy levels in human fetal brains. Using ChIP-seq and RNA-seq assays, we demonstrate that an increase in H3K79Hcy level down-regulates the expression of selected NTC-related genes including Cecr2, Smarca4, and Dnmt3b. In human NTDs brain tissues, decrease in expression of CECR2, SMARCA4, and DNMT3B is also detected along with high levels of Hcy and H3K79Hcy. Our results suggest that higher levels of Hcy contribute to the onset of NTDs through up-regulation of histone H3K79Hcy, leading to abnormal expressions of selected NTC-related genes.

Min Zhang, YiRan Wu, ZhaoXu Lu, MeiYan Song, XiaoLan Huang, LaLa Mi, Jian Yang, Xiaodai Cui. Clin Psychopharmacol Neurosci 2023;21:240-51. https://doi.org/10.9758/cpn.2023.21.2.240

Disorders of folic acid metabolism during pregnancy lead to fetal neural tube de-fects (NTDs). However, the mechanisms still require further investigation. Here, we aim to analyze the brain metabolic profiles of 30 NTDs and 30 healthy fetuses. Our results indicated that low-folate diet during early life played a causal role in cerebral metabolism, especially in lipometabolic disturbance, highlighting the importance of folate in modulating brain development and metabolism. Next, we established a mouse model of NTDs. Interestingly, the differential metabo-lites are mainly involved in glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids both in human and mice fetal brain. Since intestinal mi-crobes could critically regulate neurofunction via the intestinal-brain axis, we further found the abundances of Firmicutes and Bacteroidetes in the gut of preg-nant mice were correlated with the abundances of lipid metabolism related metabolites in the fetal brain. This finding probably reflects the intergenerational microbial-metabolism biomarkers of NTDs.

Several observational studies have reported associations between low levels of fat-soluble vitamins (A, D and E) and the incidence of pneumonia. Whether infection affects or negatively regulates serum vitamin levels remains controversial. Our aims were to develop and validate a simple-pretreatment and fast method to determine the serum levels of selected fat-soluble vitamins, namely vitamin A (retinol), vitamin D (25-OH-D₃, 25-OH-D₂, and 3-epi-25-OH-D₃), and vitamin E (α-tocopherol), in children suffering from pneumonia during the acute phase and after inflammatory marker recovery. The sample preparation procedure involving protein precipitation and filtration was finished in one step, and separation took 8 min per sample. The calibrations were linear, with R² > 0.99. Both the intra-run (n = 6) and inter-run (n = 3) precision (relative standard deviation, RSD%) values were below 14.61%. The spiked recoveries at 3 concentrations ranged from 80.97 to 111.91%. Accuracies were calibrated using both National Institute of Standards and Technology serum (NIST 968f) and external quality assurance (EQA) samples offered by the National Center of Clinical Laboratories of China, and the relative error (RE%) values ranged from −13.17% to 12.53%. Clinical sample analysis revealed that infection did alter the serum retinol concentration and it did not alter the 25-OH-D and α-tocopherol levels in young children with pneumonia.