Temporal Dynamics of Plasma Catecholamines, Metabolic and Immune Markers, and the Corticosterone:DHEA Ratio in Farmed Crocodiles before and after an Acute Stressor.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone (CORT), dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to the baseline. Downstream effects of these catecholamines and CORT appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to the baseline by the final measurement. DHEA, which is used in a ratio with CORT, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to our understanding of crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

GPAT3 deficiency attenuates corticosterone-caused hepatic steatosis and oxidative stress through GSK3ß/Nrf2 signals.

The development of nonalcoholic fatty liver disease (NAFLD) may worsen due to chronic stress or prolonged use of glucocorticoids. Glycerol-3-phosphate acyltransferase 3 (GPAT3), has a function in obesity and serves as a key rate-limiting enzyme that regulates triglyceride synthesis. However, the precise impact of GPAT3 on corticosterone (CORT)-induced NAFLD and its underlying molecular mechanism remain unclear. For our in vivo experiments, we utilized male and female mice that were GPAT3-/- and wild type (WT) and treated them with CORT for a duration of 4 weeks. In our in vitro experiments, we transfected AML12 cells with GPAT3 siRNA and subsequently treated them with CORT. Under CORT-treated conditions, the absence of GPAT3 greatly improved obesity and hepatic steatosis while enhancing the expression of genes involved in fatty acid oxidation, as evidenced by our findings. In addition, the deletion of GPAT3 significantly inhibited the production of reactive oxygen species (ROS), increased the expression of antioxidant genes, and recovered the mitochondrial membrane potential in AML12 cells treated with CORT. In terms of mechanism, the absence of GPAT3 encouraged the activation of the glycogen synthase kinase 3ß (GSK3ß)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which served as a defense mechanism against liver fat accumulation and oxidative stress. Furthermore, GPAT3 expression was directly controlled at the transcriptional level by the glucocorticoid receptor (GR). Collectively, our findings suggest that GPAT3 deletion significantly alleviated hepatic steatosis and oxidative stress through promoting GSK3ß/Nrf2 signaling pathways.

Stress-induced Neuroinflammation of the Spinal Cord is Restrained by Cort113176 (Dazucorilant), A Specific Glucocorticoid Receptor Modulator.

Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing´ syndrome and neurodegenerative disorders of humans and models of human diseases. ."The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNFα, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1ß and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1ß, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders.

Microarray evidence that 8-cell human embryos express some hormone family members including oxytocin.

OBJECTIVE: This study is to discover hormone pathways active in early cleaving human embryos. METHODS: A list of 152 hormones and receptors were compiled to query the microarray database of mRNAs in 8-cell human embryos, two lines of human embryonic stem cells plus human fibroblasts before and after induced pluripotency. RESULTS: Over half of the 152 hormones and receptors were silent on the arrays of all cell types, and more were detected at high or moderate levels on the 8-cell arrays than on the pluripotent cell or fibroblast arrays. Eight hormone family genes were uniquely detected at least 22-fold higher on the 8-cell arrays than the stem cell arrays: AVPI1, CCK, CORT, FSTL4, GIP, GPHA2, OXT, and PPY suggesting novel roles for these proteins in early development. Oxytocin was detected by pilot immunoassay in culture media collected from Day 3 embryos. Robust detection of CRHR1 and EPOR suggests the 8-cell embryo may be responsive to maternal CRH and EPO. The over-expression of POMC and GHITM suggests POMP peptide products may have undiscovered roles in early development and GHITM may contribute to mitochondrial remodeling. Under-detected on the 8-cell arrays at least tenfold were two key enzymes in steroid biosynthesis, DHCR24 and FDPS. CONCLUSIONS: The 8-cell human embryo may be secreting oxytocin, which could stimulate its own progress down the fallopian tube as well as play a role in early neural precursor development. The 8-cell embryo does not synthesize reproductive steroid hormones. As previously reported for growth factor families, the early embryo over-expresses more hormones than hormone receptors.

Early life stress aggravates disease pathogenesis in mice with experimental autoimmune encephalomyelitis: Support for a two-hit hypothesis of multiple sclerosis etiology.

Vision problems are one of the earliest diagnosed symptoms of multiple sclerosis (MS). The onset and progression of vision loss and the underlying pathogenesis in MS may be influenced by cumulative psychophysiological stress. Here, we used a two-hit model of stress in female mice to determine if early life stress (ELS, the first hit) influences the response to an immunization that induces experimental autoimmune encephalomyelitis (EAE, the second hit) later in life. We hypothesized that ELS caused by animal transportation from a vendor during early postnatal development represents a co-factor which can exacerbate the clinical severity of EAE. Indeed, adult EAE mice with a history of ELS displayed more severe clinical signs and delayed recovery compared to non-stressed EAE mice. ELS also diminished visual acuity measured by optokinetic responses, as well as locomotion and exploratory behaviours in EAE mice. Notably, ELS accelerated vision loss and caused earlier onset of visual impairments in EAE. Exacerbated functional impairments in stressed EAE mice were highly correlated with circulating corticosterone levels. The findings show that the progression of induced EAE in adulthood can be significantly impacted by adverse early life experiences. These observations emphasize the importance of comprehensive behavioural testing, including non-motor functions, to enhance the translational value of preclinical animal models of MS. Moreover, shipment stress of laboratory animals should be considered a necessary variable in preclinical MS research. The consideration of cumulative lifetime stresses provides a new perspective of MS pathogenesis within a personalized medicine framework.

In vivo synaptic potency, short-term and long-term plasticity at the hippocampal Schaffer collateral-CA1 synapses: Role of different light-dark cycles in male rats.

The changes in the light-dark(L/D) cycle could modify cellular mechanisms in some brain regions. The present study compared the effects of various L/D cycles on invivo synaptic potency, short-term and long-term plasticity in the hippocampal CA1 area, adrenal glands weight(AGWs), corticosterone (CORT) levels, and body weight differences(BWD) in male rats. Male rats were assigned into different L/D cycle groups: L4/D20, L8/D16, L12/D12(control), L16/D8, and L20/D4. The slope, amplitude, and the area under curve(AUC) related to the field excitatory postsynaptic potentials(fEPSPs) were assessed, using the input-output(I/O) functions, paired-pulse(PP) responses at different interpulse intervals, and after the induction of long-term potentiation(LTP) in the hippocampal CA1 area. Also, the CORT levels, AGWs, and BWDs were measured in all groups. The slope, amplitude, and AUC of fEPSP in the I/O functions, all three phases of PP, before and after the LTP induction, were significantly decreased in all experimental groups, especially in the L20/D4 and L4/D20 groups. As such, the CORT levels and AGWs were significantly increased in all experimental groups, especially in the L20/D4 group. Overall, the uncommon L/D cycles (minimum and particularly maximum durations of light) significantly reduced the cellular mechanism of learning and memory. Also, downtrends were observed in synaptic potency, as well as short-term and long-term plasticity. The changes in PP with high interpulse intervals, or activity of GABAB receptors, were more significant than the changes in other PP phases with different L/D durations. Additionally, the CORT levels, adrenal glands, and body weight gain occurred time-independently concerning different L/D lengths.

Naringenin and apigenin ameliorates corticosterone-induced depressive behaviors.

Background: Depression is a common kind of mental illness, and it becomes the main health burden in the world. Purpose: The aim of this study was to investigate the antidepressant effects of naringin and apigenin isolated from Chrysanthemum morifolium Ramatis. Methods: Firstly, 20 mg/kg corticosterone (CORT) was injected into mice to establish an in vivo model of depression. After treated with different dosages of naringenin and apigenin for 3 weeks, the mice underwent a series of behavioral experiments. Following this, all mice were sacrificed and biochemical analyses were performed. Subsequently, CORT (500 µM) induced PC12 cells was used as an in vitro model of depression, and lipopolysaccharide (LPS) (1 µg ml-1) induced N9 microglia cells was used as an in vitro model of neuroinflammation in N9 microglia cells, to investigate the neuroprotective mechanisms of naringenin and apigenin. Results: Results showed that the naringenin and apigenin treatment ameliorated CORT-induced sucrose preference decrease and immobility time increase, elevated the 5-hydroxytryptamine(5-HT), dopamine (DA) and norepinephrine (NE) levels, and enhanced the cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) protein expressions in the hippocampus. The results showed that the naringenin and apigenin treatment improved the PC-12 cell viability through reducing apoptosis rate induced by CORT. Furthermore, naringenin and apigenin were able to inhibit the activation of N9 cells after LPS induction, and shift microglia from proinflammatory M1 microglia toward anti-inflammatory M2 microglia, as evidenced by the decreased ratio of M1 type microglia marker CD86 and M2 type microglia marker CD86. Conclusion: These results suggested that naringenin and apigenin may improve depressive behaviors through promoting BDNF and inhibiting neuroinflammation and neuronal apoptosis.

Estrogen receptor beta in the central amygdala regulates the deleterious behavioral and neuronal consequences of repeated social stress in female rats.

While over 95% of the population has reported experiencing extreme stress or trauma, females of reproductive age develop stress-induced neuropsychiatric disorders at twice the rate of males. This suggests that ovarian hormones may facilitate neural processes that increase stress susceptibility and underlie the heightened rates of these disorders, like depression and anxiety, that result from stress exposure in females. However, there is contradicting evidence in the literature regarding estrogen's role in stress-related behavioral outcomes. Estrogen signaling through estrogen receptor beta (ERß) has been traditionally thought of as anxiolytic, but recent studies suggest estrogen exhibits distinct effects in the context of stress. Furthermore, ERß is found abundantly in many stress-sensitive brain loci, including the central amygdala (CeA), in which transcription of the vital stress hormone, corticotropin releasing factor (CRF), can be regulated by an estrogen response element. Therefore, these experiments sought to identify the role of CeA ERß activity during stress on behavioral outcomes in naturally cycling, adult, female Sprague-Dawley rats. Rats were exposed to an ethological model of vicarious social stress, witness stress (WS), in which they experienced the sensory and psychological aspects of an aggressive social defeat encounter between two males. Following WS, rats exhibited stress-induced anxiety-like behaviors in the marble burying taskand brain analysis revealed increased ERß and CRF specifically within the CeA following exposure to stress cues. Subsequent experiments were designed to target this receptor in the CeA using microinjections of the ERß antagonist, PHTPP, prior to each stress session. During WS, estrogen signaling through ERß was responsible for the behavioral sensitization to repeated social stress. Sucrose preference, acoustic startle, and marble burying tasks determined that blocking ERß in the CeA during WS prevented the development of depressive-, anxiety-like, and hypervigilant behaviors. Additionally, brain analysis revealed a long-term decrease of intra-CeA CRF expression in PHTPP-treated rats. These experiments indicate that ERß signaling in the CeA, likely through its effects on CRF, contributes to the development of negative valence behaviors that result from exposure to repeated social stress in female rats.

A Japanese case of the reincarnation type with written records made before verifications: A child claiming to have fought on the battleship Yamato.

This paper reports a case of the reincarnation type in which a child claims to have past-life memories and exhibits behaviors appropriate to the person he appears to be referring to as his past-life personality. The case has the following three interesting characteristics. First, it is a fairly strong Japanese case in the sense that it has many of the characteristic features of cases of the reincarnation type. Second, the child's statements were recorded and the investigation started before the possible identification of the previous personality was made. Third, in a number of ways, it is comparable to the case of James Leininger, one of the best-known American cases: The child claimed to have fought in the Second World War and have been killed in a battle; had unusual knowledge about a battleship with which he claimed to have been affiliated; and repeated in a play the crucial scene of the battle in which he claimed to have died.

Behavior and adrenal physiology of Magellanic penguins (Spheniscus magellanicus) serving as ambassador animals.

Ambassador animals are part of many zoo programs, but studies assessing their impact on these animals are relatively rare. This study validated an excrement glucocorticoid metabolite (GCM) assay for Magellanic penguins and used GCM measures in conjunction with behavioral observations to evaluate individual responses to participation in an ambassador animal program. Excrement samples and behavioral observations were collected daily from each bird during two phases, 1 week during which it participated in a twice-daily ambassador program and 1 week in which it did not. We found no differences in GCMs between phases or in comparisons between penguins with 5 or 10 years of program experience. GCM also did not show significant individual variation and did not increase over time during the program phase. There were no significant correlations between bird experience and behavior frequencies, nor GCM concentrations and behavior, across birds. We observed significant positive correlations between the penguins' engagement with novel objects during programs and their unguided approach to guests. Our results suggest that there is no adverse physiological effect of program participation on these penguins, that behavioral and physiological responses may be decoupled, and that choice and control can increase desired behaviors behavior during ambassador programs.

Puerarin alleviates depressive-like behaviors in high-fat diet-induced diabetic mice via modulating hippocampal GLP-1R/BDNF/TrkB signaling.

OBJECTIVE: Depression is one of the most common complications in patients with diabetes. Our previous study demonstrated puerarin, a dietary isoflavone, improved glucose homeostasis and ß-cell regeneration in high-fat diet (HFD)-induced diabetic mice. Here, we aim to evaluate the potential effect of puerarin on diabetes-induced depression. METHODS: The co-occurrence of diabetes and depression with related biochemical alterations were confirmed in HFD mice and db/db mice, respectively using behavioral analysis, ELISA and western blotting assay. Furthermore, impacts of puerarin on depression-related symptoms and pathological changes were investigated in HFD mice. RESULTS: The results showed that puerarin effectively alleviated the depression-like behaviors of HFD mice, down-regulated serum levels of corticosterone and IL-1ß, while up-regulated the content of 5-hydroxytryptamine. Simultaneously, puerarin increased the number of hippocampal neurons in HFD mice, and suppressed the apoptosis of neurons to protect the hippocampal neuroplasticity. GLP-1R expression in hippocampus of HFD mice was enhanced by puerarin, which subsequently activated AMPK, CREB and BDNF/TrkB signaling to improve neuroplasticity. Importantly, our data indicated that puerarin had an advantage over fluoxetine or metformin in treating diabetes-induced depression. CONCLUSION: Taken together, puerarin exerts anti-depressant-like effects on HFD diabetic mice, specifically by improving hippocampal neuroplasticity via GLP-1R/BDNF/TrkB signaling. Puerarin as a dietary supplement might be a potential candidate in intervention of diabetes with comorbid depression.

Chemogenetic activation of PVN CRH neurons disrupts the estrous cycle and LH dynamics in female mice.

Introduction: The impact of stress on reproductive function is significant. Hypothalamic paraventricular nucleus (PVN) corticotrophin-releasing hormone (CRH) plays a major role in regulating the stress response. Understanding how the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis interact is crucial for comprehending how stress can lead to reproductive dysfunction. However, whether stress influences reproductive function via modulating PVN CRH or HPA sequelae is not fully elucidated. Methods: In this study, we investigated the impact of chemogenetic activation of PVN CRH neurons on reproductive function. We chronically and selectively stimulated PVN CRH neurons in female CRH-Cre mice using excitatory designer receptor exclusively activated by designer drugs (DREADDs) viral constructs, which were bilaterally injected into the PVN. The agonist compound-21 (C21) was delivered through the drinking water. We determined the effects of DREADDs activation of PVN CRH neurons on the estrous cycles, LH pulse frequency in diestrus and metestrus and LH surge in proestrus mice. The effect of long-term C21 administration on basal corticosterone secretion and the response to acute restraint stress during metestrus was also examined. Additionally, computer simulations of a mathematical model were used to determine the effects of DREADDs activation of PVN CRH neurons, simulating chronic stress, on the physiological parameters examined experimentally. Results: As a result, and consistent with our mathematical model predictions, the length of the estrous cycle was extended, with an increase in the time spent in estrus and metestrus, and a decrease in proestrus and diestrus. Additionally, the frequency of LH pulses during metestrus was decreased, but unaffected during diestrus. The occurrence of the preovulatory LH surge during proestrus was disrupted. The basal level of corticosterone during metestrus was not affected, but the response to acute restraint stress was diminished after long-term C21 application. Discussion: These data suggest that PVN CRH neurons play a functional role in disrupting ovarian cyclicity and the preovulatory LH surge, and that the activity of the GnRH pulse generator remains relatively robust during diestrus but not during metestrus under chronic stress exposure in accordance with our mathematical model predictions.

[Clinical efficacy of shallow-needle therapy combined with estazolam on insomnia of liver stagnation transforming into fire pattern: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of shallow-needle therapy combined with estazolam on insomnia differentiated as liver stagnation transforming into fire and its effect on adrenocorticotropic hormone (ACTH) and cortisol (CORT), so as to explore the mechanism of this combined treatment. METHODS: A total of 119 patients with insomnia of liver stagnation transforming into fire pattern were randomly divided into shallow-needle therapy group (n=40), medication group (n=39), and shallow-needle therapy combined with medication group (combined therapy group,n=40). In the shallow-needle therapy group, the patients were treated with finger pressure and operation with shallow stimulating at Zhenjing (Dong's extra point, sedative point) and Taichong (LR3). In the medication group, the patients were administered with estazolam (1 mg) orally. In the combined therapy group, both shallow-needle therapy and medication were administered. The treatment was given once daily in each group, 10 days as one session of treatment and 2 sessions were required. Before and after the treatment, Pittsburgh sleep quality index scale (PSQI) and Self-rating anxiety scale (SAS) were used to assess sleep and anxiety status. ELISA was used to detect the contents of ACTH and CORT in plasma. The clinical efficacy was evaluated in each group. RESULTS: In within-group comparison, PSQI scores, SAS scores and the concentrations of ACTH and CORT in plasma were all decreased (P<0.05) after treatment for the patients of three groups. After treatment, the total PSQI score, the score for sleep latency, sleep duration and daytime dysfunction, as well as SAS score in the combined therapy group were all lower than those of the shallow-needle therapy group (P<0.05); the total PSQI score, the score for sleep duration and sleep efficiency, as well as SAS score were lower when compared with the medication group (P<0.05). The total effective rates were 87.50% (35/40), 82.05% (32/39) and 95.00% (38/40) in the shallow-needle therapy group, the medication group and the combined therapy group, respectively. The total effective rate in the combined therapy group was higher than those of the shallow-needle therapy group and the medication group separately (P<0.05). CONCLUSION: Shallow-needle therapy combined with estazolam is effective on insomnia of liver stagnation transforming into fire pattern, and its underlying effect mechanism is related to the reduction of plasma ACTH and CORT levels.

Posterodorsal Medial Amygdala Urocortin-3, GABA, and Glutamate Mediate Suppression of LH Pulsatility in Female Mice.

The posterodorsal subnucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. Inhibition of MePD urocortin-3 (Ucn3) neurons prevents psychological stress-induced suppression of luteinizing hormone (LH) pulsatility while blocking the stress-induced elevations in corticosterone (CORT) secretion in female mice. We explore the neurotransmission and neural circuitry suppressing the gonadotropin-releasing hormone (GnRH) pulse generator by MePD Ucn3 neurons and we further investigate whether MePD Ucn3 efferent projections to the hypothalamic paraventricular nucleus (PVN) control CORT secretion and LH pulsatility. Ucn3-cre-tdTomato female ovariectomized (OVX) mice were unilaterally injected with adeno-associated virus (AAV)-channelrhodopsin 2 (ChR2) and implanted with optofluid cannulae targeting the MePD. We optically activated Ucn3 neurons in the MePD with blue light at 10 Hz and monitored the effect on LH pulses. Next, we combined optogenetic stimulation of MePD Ucn3 neurons with pharmacological antagonism of GABAA or GABAB receptors with bicuculline or CGP-35348, respectively, as well as a combination of NMDA and AMPA receptor antagonists, AP5 and CNQX, respectively, and observed the effect on pulsatile LH secretion. A separate group of Ucn3-cre-tdTomato OVX mice with 17ß-estradiol replacement were unilaterally injected with AAV-ChR2 in the MePD and implanted with fiber-optic cannulae targeting the PVN. We optically stimulated the MePD Ucn3 efferent projections in the PVN with blue light at 20 Hz and monitored the effect on CORT secretion and LH pulses. We reveal for the first time that activation of Ucn3 neurons in the MePD inhibits GnRH pulse generator frequency via GABA and glutamate signaling within the MePD, while MePD Ucn3 projections to the PVN modulate the HPG and HPA axes.

The efficacy and safety of Jin's three-needle therapy vs. placebo acupuncture on anxiety symptoms in patients with post-stroke anxiety: A study protocol for a randomized controlled trial.

Background: A large number of clinical RCTs have verified that Jin's three-needle therapy (JTNT) has a great contribution to promoting the function of paralyzed limbs and relieving anxiety disorders for patients with post-stroke anxiety (PSA). However, there is still a lack of sham needle control, and its placebo effect cannot be ruled out. This study firstly verifies the real effectiveness of JTNT. Besides, the changes in serum indexes on the hypothalamic-pituitary-adrenal axis (HPA axis) are observed dynamically by the Enzyme-Linked ImmunoSorbent Assay (ELISA). The activation of different brain regions by JTNT is recorded using resting functional magnetic resonance imaging (rs-fMRI). Therefore, we can provide more practical and powerful evidence-based medical evidence for clinical decisions. Method: This is a 16 week parallel, single-blind, random, controlled trial, including baseline, 4 weeks of treatment, and 12 weeks of follow-up. A total of 114 participants will be randomly divided into three groups in the proportion of 1:1:1. Participants will receive Jin's three-needle therapy in the active acupuncture group and accept sham needle treatment in the sham acupuncture group. In the waitlist control group, patients will not receive any acupuncture treatment. Outcomes cover three types of indicators, including scale indicators, serum indicators, and imaging indicators. The primary outcome is the change in the performance of anxiety symptoms, which is estimated by the 14-item Hamilton Anxiety Rating Scale (HAMA-14) and the 7-item Generalized Anxiety Disorder scale (GAD-7). Secondary outcomes are physical recovery and daily quality of life, which are evaluated by the National Institute of Health stroke scale (NIHSS) and the Modified Barthel Index Score (MBI Scale). Therefore, the assessment of the scale is carried out at baseline, 2nd, 4th, 8, 12, and 16 weeks. Adrenocorticotropin and cortisol will be quantitatively detected by ELISA at baseline and 4 weeks after treatment. In addition, regional homogeneity analysis (ReHo) will be used to record the activity of brain regions at baseline and 4 weeks after intervention. Discussion: The study aims to provide high-quality clinical evidence on the effectiveness and safety of JTNT for patients with PSA. In addition, this trial explores a possible mechanism of JTNT for patients with PSA. Clinical trial registration: Chinese Clinical Trial Registry, identifier [ChiCTR2200058992].

Sex-specific stress and biobehavioral responses to human experimenters in rats.

Important factors influencing the outcome of animal experiments in preclinical research are often overlooked. In the current study, the reaction of female and male rats toward the biological sex of a human experimenter was investigated in terms of anxiety-like behaviors and physiological stress responses, as measured by infrared (IR) thermography, circulating corticosterone (CORT) and oxytocin levels. Female rats displayed consistently exacerbated anxiety-related behaviors along with elevated body surface temperature during repeated exposure to male experimenters. Experimental stress further intensified thermal responses to a male experimenter, especially in female rats. The behavioral responses to a male experimenter in females were associated with higher circulating CORT and lower oxytocin levels. Similar responses were induced by a T-shirt worn by a human male. The findings suggest that psychophysiological responses of female rats to a male experimenter are influenced by both visual and olfactory cues. The results emphasize the need to not only consider sex differences in experimental animals, but also standardize and report the experimenter's biological sex to avoid ambiguity in the generation and interpretation of results.

Short report: Gendered workplace social interaction processes in autism.

BACKGROUND: Navigating workplace social interactions can be stressful for autistic people and be experienced differently by gender. A better understanding of the autistic experience of these difficulties is needed to inform effective policy, practice, and individualized support. METHOD: Fifty-five autistic individuals (n women=32; n men=22) participated in either an online survey or focus group. Data were analyzed using inductive thematic analysis. RESULTS: The data suggests that the social and interaction expectations placed upon autistic individuals differ by gender and can contribute to occupational stress. CONCLUSIONS: The data provides a basis for further investigation considering Conservation of Resources Theory and its practical application to inform reasonable adjustments in the workplace for autistic people. WHAT THIS PAPER ADDS: The gendered workplace experiences of autistic people is an emerging area of research. However, how workplace social interactions are experienced by each gender remains under-researched. An understanding of this could help decrease occupational stress, inform reasonable adjustments, and increase labor market participation in this population. This paper adds to the existing literature in showing that workplace social interactions for autistic people are experienced differently by gender. As such, the implications in the experience of occupational stress may also differ. Therefore, the importance of having reasonable adjustments in the workplace that account for gender is highlighted.

Perceived predation risk predicts glucocorticoid hormones, but not reproductive success in a colonial rodent.

The Cort-Adaptation hypothesis suggests that elevated glucocorticoids (GCs) can facilitate an adaptive response to environmental and physiological challenges. Most previous studies have focused on avian species, which may limit their generalizability to mammals, where lactation is known to be a major physiological challenge. Furthermore, the effect of predation risk on GC levels has not been tested in the Cort-Adaptation hypothesis. We sought to test this hypothesis in a colonial prey species, black-tailed prairie dogs (Cynomys ludovicianus). We predicted that individuals located near fewer neighboring conspecifics would perceive an increased risk of predation and, in turn, have increased GCs (measured through hair cortisol concentration (HCC)) and reduced annual reproductive success compared to more centrally located individuals. We also investigated other putative influences on HCC: age, lactation status, body condition, and season of hair growth. Levels of vigilance behavior were higher for those with fewer neighboring conspecifics, suggesting variation in perceived risk of predation. Further, the risk of predation appeared to represent a chronic, detrimental stressor as evidenced by a significant increase in HCC for prairie dogs with fewer neighbors. Lactation status and season also influenced HCC. We found support for the Cort-Adaptation hypothesis where increased HCC during the reproductive season correlated with whether a female produced a litter, but not litter size, suggesting a minimum threshold of GCs is required for successful reproduction in this species. Our work illustrates that HCC may operate as an indicator of perceived predation risk, but care should be taken to consider the variety of factors influencing GC homeostasis, in particular lactation, when drawing conclusions using HCC as a marker of long-term stress.

Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats.

Background and aim: Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats. Experimental procedure: The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry. Results and conclusion: CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

Chronic restraint stress produces sex-specific behavioral and molecular outcomes in the dorsal and ventral rat hippocampus.

Stress-related disorders display differences at multiple levels according to sex. While most studies have been conducted in male rodents, less is known about comparable outcomes in females. In this study, we found that the chronic restraint stress model (2.5 h/day for 14 days) triggers different somatic responses in male and female adult rats. Chronic restraint produced a loss in sucrose preference and novel location preference in male rats. However, chronic restraint failed to produce loss of sucrose preference in females, while it improved spatial performance. We then characterized the molecular responses associated with these behaviors in the hippocampus, comparing the dorsal and ventral poles. Notably, sex- and hippocampal pole-specific transcriptional signatures were observed, along with a significant concordance between the female ventral and male dorsal profiles. Functional enrichment analysis revealed both shared and specific terms associated with each pole and sex. By looking into signaling pathways that were associated with these terms, we found an ample array of sex differences in the dorsal and, to a lesser extent, in the ventral hippocampus. These differences were mainly present in synaptic TrkB signaling, Akt pathway, and glutamatergic receptors. Unexpectedly, the effects of stress on these pathways were rather minimal and mostly dissociated from the sex-specific behavioral outcomes. Our study suggests that female rats are resilient and males susceptible to the restraint stress exposure in the sucrose preference and object location tests, while the activity of canonical signaling pathways is primarily determined by sex rather than stress in the dorsal and ventral hippocampus.