The hippocampus is a region in which neurogenesis persists and retains substantial plasticity throughout lifespan. Accumulating evidences indicate an important role of androgens and androgenic signaling in the regulation of offspring hippocampal neurogenesis and the survival of mature or immature neurons and gliocyte. Hyperandrogenic disorders have been associated with depression and anxiety. Previous studies have found that pregnant hyperandrogenism may increase the susceptibility of the offspring to depression or anxiety and lead to abnormal hippocampal neurogenesis in rats. In this study, pregnant rats were given subcutaneous injection of aromatase inhibitor letrozole in order to establish a maternal hyperandrogenic environment for the fetal rats. The lithium chloride (LICl) was used as an intervention agent since a previous study has shown that lithium chloride could promote neurogenesis in the hippocampus. The results revealed that pregnant administration of letrozole resulted in depressive- and anxious-like behaviors in the adolescent period. A remarkable decrease in immature nerve cells marked by doublecortin and mature neurons co-expressed by Brdu and NeuN in adult years were detected in the hippocampal dentate gyrus of adolescent rats. Lithium chloride alleviated the effects on neurobehavioral and promoted the differentiation and proliferation of neural progenitor cells, while a hyperandrogenic intrauterine environment had no effects on astrocytes marked by GFAP in the dentate gyrus. Furthermore, the Wnt/β-catenin signaling pathway related to normal development of hippocampus was examined but there was no significant changes in Wnt signaling pathway members. Our study provides evidence that exposure of androgen during pregnancy leads to alterations in depressive, anxious and stereotypical behaviors and these phenotypes are possibly associated with changes in neurogenesis in the dentate gyrus.

Background: The two main symptoms at high altitude, sleep abnormalities and cognitive impairments, interact with each other. These two dysfunctions are also closely related to systemic multisystem diseases, including cerebrovascular diseases, psychiatric disorders, and immune regulatory diseases.Purpose: To systematically analyze and visualize research on sleep disturbances and cognitive impairment at high altitudes using a bibliometrics method, and to determine future research directions by analyzing research trends and the latest hotspots.Methods: Publications from 1990 to 2022 on sleep disturbances and cognitive impairment at high altitudes were retrieved from the Web of Science. Using the R Bibliometrix software and Microsoft Excel, all data were examined statistically and qualitatively. For network visualization, the data were later exported into VOSviewer 1.6.17 and CiteSpace 6.1.R6.Results: A total of 487 articles in this area were published from 1990 to 2022. In this period, there was an overall increase in the number of publications. The United States has shown considerable importance in this sector. Bloch Konrad E was the most prolific and valuable author. The most prolific journal was High Altitude Medicine & Biology, and it has been the first choice for publishing in this field in recent years. Analysis of keyword co-occurrences suggested that research interest in the clinical manifestations of sleep disturbances and cognitive impairment caused by altitude hypoxia was mainly focused on “acute mountain-sickness,” “insomnia,” “apnea syndrome,” “depression,” “anxiety,” “Cheyne-strokes respiration,” and “pulmonary hypertension.” The mechanisms of disease development related to “oxidative stress,” “inflammation,” “hippocampus,” “prefrontal cortex,” “neurodegeneration,” and “spatial memory” in the brain have been the focus of recent research. According to burst detection analysis, “mood” and “memory impairment,” as terms with high strength, are expected to remain hot topics in the coming years. High-altitude-induced pulmonary hypertension is also in the emerging stage of research, and the treatments will continue to receive attention in the future.Conclusion: More attention is being focused on sleep disturbances and cognitive impairment at high altitudes. This work will serve as a useful reference for the clinical development of treatments for sleep disturbances and cognitive impairment induced by hypobaric hypoxia at high altitudes.

This study investigated the effects of gastrodin (GAS) on analgesic, anxiolytic, ferroptosis, and jejunal microbiota in chronic inflammatory pain mice. The chronic inflammatory pain model of C57BL/6J mice was established by hindpaw injection of complete Freund’s adjuvant (CFA). After GAS treatment, thermal hyperalgesia test, mechanical allodynia test, elevated plus-maze (EPMT), and open-field test (OFT) were performed to assess the behavioral changes of pain and anxiety. mRNAs of FTHI, GPX4, HO-1, and PTGS2 and jejunal microbiota were measured by qPCR. In CFA-injected C57BL/6 mice, we found that the mechanical and thermal pain threshold were increased with treatment of GAS. In EPMT, the number of entries in open arms and retention times of open arms were increased by GAS. In the OFT, the time spent in the central area was also increased. Furthermore, GAS enhanced mRNA expressions of FTHI, GPX4, and HO-1 but decreased the expression of PTGS2 in a dose-dependent manner. GAS is effective in the treatment of mice chronic inflammatory pain and anxiety-like behaviors. It may be exhibits potential neuroprotective effects through inhibition of ferroptosis independently of the intestinal microbiota.