In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.
Flos Lonicerae Japonicae (FLJ) is a popular herb used for many centuries in Traditional Chinese Medicine as a treatment of fever and inflammation. Non-fumigated processing of FLJ has been the traditional approach used in post-harvest preparation of the commodity for commercial use. However, in recent years, natural drying processing of FLJ has been replaced by sulfur-fumigation for efficiency and pest control. Sulfur-fumigation can induce changes in the volatile compounds of the herb, altering its medicinal properties. A comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF/MS) method was established for the resolution and determination of volatile components in non-fumigated and sulfur-fumigated FLJ. In this paper, analysis of the volatile oils in non-fumigated and sulfur-fumigated (including lab-prepared sulfur- fumigated and industrial sulfur-fumigated) FLJ was performed using GC×GC-TOF/MS. Seventy-three representative volatile components were identified, including furans, alkalies, acids, aldehydes, ketones, alcohols, terpenes, esters, and others, as the main components of FLJ volatile oils. The proposed method was successfully applied for rapid and accurate quality evaluation of FLJ and its related medicinal materials and preparations.