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Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with high morbidity and great social and economic relevance. However, extant pharmacotherapies of PTSD require long-term use to maintain effectiveness and have enormous side effects. The glutamatergic system, especially the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), is an important target of current research on the mechanism of PTSD. Postsynaptic AMPAR function and expression are known to be increased by (2R, 6R)-hydronorketamine (HNK), the primary metabolite of ketamine. However, whether (2R,6R)-HNK alleviates PTSD-like effects via AMPAR upregulation is yet to be known.In the present study, rats were exposed to single prolonged stress and electric foot shock (SPS&S). Afterwards, gradient concentrations of (2R,6R)-HNK (20, 50, and 100 μM) were administered by intracerebroventricular (i.c.v.) injection. Open field, elevated plus maze, freezing behavior, and forced swimming tests were used to examine PTSD-like symptoms. In addition, the protein levels of GluA1, BDNF and PSD-95 were analyzed using western blotting and immunofluorescence, and the synaptic ultrastructure of the prefrontal cortex (PFC) was observed by transmission electron microscopy.We found that (2R,6R)-HNK changed SPS&S-induced behavioral expression, such as increasing autonomous activity and residence time in the open arm and decreasing immobility time. Likewise, (2R,6R)-HNK (50 μM) increased GluA1, BDNF, and PSD-95 protein expression in the PFC. Changes in synaptic ultrastructure induced by SPS&S were reversed by administration of (2R,6R)-HNK. Overall, we find that (2R,6R)-HNK can ameliorate SPS&S-induced fear avoidance in rats, as well as rat cognates of anxiety and depression. This may be related to GluA1-mediated synaptic plasticity in the PFC.

The drought resistance mechanism of typical mosses in the karst area was studied, and the water and photosynthetic physiological adaptation of mosses to karst environmental change was analyzed in this paper, which provided the basis for the restoration and control of karst rocky desertification ecological environment. Three superior plants in the rocky desertification area of Guizhou province were selected; they are, respectively, Erythrodontium julaceum (Schwaegr.) Par., Barbula unguiculata Hedw., and Bryum argenteum Hedw. Results show that the three kinds of plant rock mosses of leaf water potential (Ψs), free water content (Va), total water content, and relative water content (RWC) decreased; bound water (Vs), water saturation deficit (WSD), and Vs/Va ratio increased; transpiration rate (Tr) fell slightly, under drought stress. The physiological indexes of water have different degrees of recovery after rehydration. The total chlorophyll content shows a trend of first increasing followed by falling and then rising. RWC was negatively related to qN and positively related to Fv/Fm, yield, ETR, and qP. After rewetting, the fluorescence parameters are returned to average level under mild-to-moderate stress. At the same time, it is hard to get back to the control level under severe pressure. The water use efficiency (WUE) decreased with stress and recovered to different degrees after rehydration.

As an adverse form of early-life stress (ELS), maternal separation (MS) can interfere with the development of cognition and behaviors of adolescent rodents. Brain-derived neurotrophic factor (BDNF) is involved in the regulation of brain development and function, but the molecular mechanisms by which BDNF regulates brain function and behavior in MS with different stressor strengths remain unclear. This descriptive study characterized the levels of BDNF in the prefrontal cortex (PFC) and plasma corticosterone (CORT) from the offspring of rats exposed to early handling (EH, 15-min separation per day) and prolonged MS (PMS, 180-min separation per day), during postnatal days (PND) 1‑21. The behavioral and biochemical analyses were performed during adolescence (PND 42‑56). PMS resulted in reduced weight and decreased locomotor activity in the open field test and Y-maze task compared to control (CON) group, with EH showing an intermediate phenotype. BDNF protein levels in the PFC were lower in PMS compared to EH and further reduced in CON male rats. Plasma CORT levels were higher in PMS compared to CON with EH again showing intermediate levels. Neither PMS or EH affected spatial learning in the Y-maze task. These findings indicate that longer periods of maternal separation are necessary to increase anxiety-like behavior, elevate CORT levels, and further suppress BDNF levels in the PFC, providing a possible mechanism to explain why more severe forms of ELS lead to more significant psychiatric and medical consequences later in life.

By using the Hawking Taub-NUT metric, this note gives an explicit construction of a 3-parameter family of Einstein Finsler metrics of non-constant flag curvature in terms of navigation representation.

Background: Cognitive decline is one of the core symptoms of a variety of mental diseases. How to improve cognitive function is one of the key issues in psychiatric research. Stress, especially early-life stress, increases the prevalence of mental diseases in adult, and is often accompanied by hippocampal- related cognitive dysfunctions. However, its pathological mechanism remains unclear. Abnormal functioning of Brain-derived neurotrophic factor (BDNF) signaling pathway may be one of the mechanisms. Although the abnormal BDNF-TrkB signaling system have been found in hippocampus of the early-life stressed mice, but whether and how it mediates the cognitive dysfunction needs to be further explored. Aims & Objectives: To figure out the role of hippocampus BDNFTrkB signaling system in mediating the cognitive dysfunction caused by early-life stress, we constructed an stress model of restricted nesting materials and bedding materials in mice. Method: Early stress models of restricted nesting materials and bedding were constructed from day 2 to day 9 after birth, and cognitive behavioral tests and molecular biological tests were performed in adult mice. SOR test and Y maze test were used to evaluate the spatial learning and memory ability and spatial working memory ability of mice. Immunohistochemical staining and immunofluorescence staining techniques were used to quantitatively evaluate the expression of BDNF protein in the hippocampus of mice and the number of adult neurons generated in the DG region. To specifically downregulate the expression of BDNF in the DG region of the mouse hippocampus, AAV2/9-CaMKIIa-Crevirus was injected into the brain of the Bdnftm2Jae/J mice. To specifically up-regulate BDNF in DG, Recombinant Human BDNF (rhBDNF, 0.5 µ g/µ l, 0.5 µ l/site) were injected directly into the brain by microinjection. To further activate or inhibit the BDNF-TrkB signaling pathway in the hippocampal DG region of mice, TrkB receptor agonist 7,8-DHF (1µ g/µ l, 0.5µ l/site) or antagonist ANA-12 (1µ g/µ l, 0.5µ l/site) were injected directly into the brain by microinjection, respectively. Intraperitoneal injection of 7,8-DHF (5 mg/kg), and ANA- 12 (0.5 mg/kg) for validation and supplementation of brain region injection. Results: Adopting the limited nesting and bedding material paradigm, we first demonstrated that ELS impaired spatial memory, suppressed BDNF expression and neurogenesis in DG in adult mice. Down- regulating BDNF expression (conditional BDNF knockdown) or inhibition of the TrkB receptor (using its anatognist ANA-12) in the DG mimicked the cognitive deficits of ELS. Acute up-regulation of BDNF (exogenous human recombinant BDNF microinjection) levels or activation of TrkB receptor (using its agonist, 7,8-DHF) in the DG restored ELS-induced spatial memory loss. Finally, acute and subchronic systemic administration of 7,8-DHF successfully restored spatial memory loss in stressed mice. Subchronic 7,8-DHF treatment also reversed ELSinduced neurogenesis reduction. Discussion & Conclusion: Our results suggest that BDNF and its TrkB receptor are causally involved in the cognitive impairment caused by early-life stress. More importantly, our results of subchronic systemic administration of 7,8-DHF highlight the BDNF-TrkB pathway as the potential therapeutic targets for the treatment of cognitive deficits in stress-related psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidences suggest that trace amineassociated receptor 1 (TAAR1) is a new promising target for psychiatric disorders since TAAR1 was discovered in 2001[1, 2]. Stressful life events are a key environmental risk factor to develop major depressive disorder (MDD) [3]. Studies in humans and animals have demonstrated that depression and stress induced pathologies are implicated in the dentate gyrus (DG), one of the key regions for HPA axis glucocorticoid feedback [4]. TAAR1 exhibits widespread expression in the hippocampus and the data gained in transcriptomic data that indicate an important role of TAARs in the regulation of adult neurogenesis [5]. However, the role of TAAR1 in dentate gyrus (DG) mediating the negative outcomes induced by chronic stress remains unknown. Aims & Objectives: In this study, we aimed to investigate the role of TAAR1 involved in stress-induced structural and functional impairments of the DG. Methods: Firstly, chronic social defeat stress model (21 days) in mice was established. Via behavioral measurement and molecular biology techniques, hippocampus-related behaviors, adult neurogenesis, the expression levels of TAAR1 induced by chronic social defeat stress were investigated. Secondly, we explored whether selective knockout TAAR1 in the dentate gyrus (DG) can mimic the chronic stress induced impaired adult neurogenesis and cognitive function deficits. A Cre recombinase-responsive adeno-associated virus (AAV) was bilaterally stereotactically microinjected into the DG of TAAR1 CKO mice. Lastly, we investigated whether and how activating TAAR1 during stress exposure could block the negative outcomes of chronic stress exposure. RO5263397, a TAAR1 agonist, prior to each stress exposure were systematically administered. Results: Male C57BL/6N mice subjected to chronic social defeat stress exhibited significant reduction in the TAAR1 mRNA level in the DG, impaired social approach behavior, social memory and spatial object recognition memory, and impaired proliferation and maturation of adult-born dentate granule cells. Furthermore, selective knockout TAAR1 in the DG can mimic the chronic stress induced hippocampus- dependent cognitive function deficits and damage of neurogenesis. Lastly, Systemic TAAR1 agonist RO5263397 administration during chronic stress exposure prevented stress-induced deficits of hippocampus-dependent cognitive ability. RO5263397 reversed the inhibitory effects on adult neurogenesis induced by chronic stress and alleviated chronic stress-evoked morphological changes of dental granule cells, including dendrite retraction, shrinkage of apical branches and spine loss. Discussion & Conclusion: Taken together, our findings indicate TAAR1 is an important molecular mediating chronic stress-induced deficit of hippocampal morphology and function. The TAAR1 agonist RO5263397 has the potential role towards the treatment of patients with MDD-related cognitive impairments. [ABSTRACT FROM AUTHOR]

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Background and purpose: Histological grading based on the degree of differentiation has limitations in evaluating the biological behavior of colorectal cancer. Finding more morphological indicators will provide more evidence for the prognosis and stratified management of colorectal cancer. This study aimed to investigate the relationship between poorly differentiated clusters (PDC) and clinicopathological parameters in colorectal adenocarcinoma and its significance. Methods: Data of 101 patients with colorectal adenocarcinoma who underwent radical surgical resection in Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2019 to October 2020 were collected. Among them, there were 54 males and 47 females, ranging in age from 29 to 86 years with median age of 62 years. Tumor size ranged from 1.5 to 9.0 cm (mean 4.5 cm). There were 42 cases of left colon cancer, 21 cases of right colon cancer and 38 cases of rectal cancer. The number of PDC of colorectal adenocarcinoma in H-E section was observed under light microscope and graded, and the relationship between PDC grade and other clinicopathological parameters of colorectal adenocarcinoma was analyzed. Results: Among 101 cases of colorectal adenocarcinoma, 42 cases (41.6%) were G1 grade, 29 cases (28.7%) were G2 grade, and 30 cases (29.7%) were G3 grade. In colorectal adenocarcinoma, PDC was positively correlated with histological grade, invasion depth, lymph node metastasis, lymphovascular invasion, nerve invasion, distant metastasis stage and tumor budding (TB) (P ＜ 0.05), but not with patient age, gender, tumor site or tumor size (P ＞ 0.05). Conclusion: PDC is closely related to the invasive biological behavior of colorectal adenocarcinoma. PDC is likely to be a more effective prognostic marker than traditional histological grading after TB. Identification and evaluation of PDC grading in colorectal adenocarcinoma can better predict the biological behavior of colorectal adenocarcinoma, and thus more accurately guide the treatment and prognosis evaluation of colorectal cancer.