Fluorene-9-bisphenol acts on the gut-brain axis by regulating oxytocin signaling to disturb social behaviors in zebrafish.

Previous studies have identified the exposure to ubiquitous environmental endocrine disruptors may be a risk factor of neurological disorders. However, the effects of fluorene-9-bisphenol (BHPF) in environmental exposure concentrations associated with these disorders are poorly understood. In this study, classic light-dark and social behavior tests were performed on zebrafish larvae and adults exposed BHPF exposure to evaluate social behavioral disorders and the microbiota-gut-brain axis was assessed to reveal the potential mechanisms underlying the behavioral abnormalities observed. Our results demonstrated that zebrafish larvae exposed to an environmentally relevant concentration (0.1 nM) of BHPF for 7 days showed a diminished response to external environmental factors (light or dark). Zebrafish larvae exposed to BHPF for 7 days or adults exposed to BHPF for 30 days at 1 µM displayed significant behavioral inhibition and altered social behaviors, including social recognition, social preference, and social fear contagion, indicating autism-like behaviors were induced by the exposure. BHPF exposure reduced the distribution of Nissl bodies in midbrain neurons and significantly reduced 5-hydroxytryptamine signaling. Oxytocin (OXT) levels and expression of its receptor oxtra in the gut and brain were down-regulated by BHPF exposure. In addition, the expression levels of genes related to the excitation-inhibitory balance of synaptic transmission changed. Microbiomics revealed increased community diversity and altered abundance of some microflora, such as an elevation in Bacillota and Bacteroidota and a decline in Mycoplasmatota in zebrafish guts, which might contribute to the abnormal neural circuits and autism-like behaviors induced by BHPF. Finally, the rescue effect of exogenous OXT on social behavioral defects induced by BHPF exposure was verified in zebrafish, highlighting the crucial role of OXT signaling through gut-brain axis in the regulatory mechanisms of social behaviors affected by BHPF. This study contributes to understanding the effects of environmental BHPF exposure on neuropsychiatric disorders and attracts public attention to the health risks posed by chemicals in aquatic organisms. The potential mental disorders should be considered in the safety assessments of environmental pollutants.

Melatonin protects zebrafish pancreatic development and physiological rhythms from sodium propionate-induced disturbances via the hypothalamic-pituitary-thyroid axis.

BACKGROUND: The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS: In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic-pituitary-thyroid axis were significantly altered. Melatonin at a concentration of 1 µmol L-1, with a mild effect on zebrafish, observably alleviated sodium propionate-induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION: Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate-induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry.

The deleterious effects and potential therapeutic strategy of fluorene-9-bisphenol on circadian activity and liver diseases in zebrafish and mice.

Increasing evidence indicates that disturbance of the clock genes, which leads to systemic endocrine perturbation, plays a crucial role in the pathogenesis of metabolic and liver diseases. Fluorene-9-bisphenol (BHPF) is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown. The impacts and involved mechanisms of BHPF on the liver diseases, metabolism, and circadian clock were comprehensively studied by zebrafish and mouse models. The therapeutic effect of melatonin (MT) was also verified. Zebrafish and mouse models with either acute exposure (0.5 and 1 µmol/L, 1-4 days post-fertilization) or chronic oral exposure (0.5 and 50 mg/(kg·2 days), 30 days) were established with various BHPF concentrations. Herein, we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model. BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain. The liver sexual dimorphic alteration along with reduced growth hormone and estrogens played a critical role in damaged glucose metabolism, hepatic inflammation, and fibrosis induced by BHPF. Besides, sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice. We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for liver metabolism disorders associated with endocrine perturbation chemicals. These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.

Inhibition of voltage-gated sodium ion channel by corannulene and computational inversion blockage underlying mechanisms.

Corannulene (Cor), a special carbon material, evidenced strong protein binding capacity which regulating lysozyme crystallization and controlling reactive oxygen species (ROS) generation. Ion channel protein play role in regulating ion channel functions to affect physiological functions. However, the interaction between Cor and ion channel protein have not been studied. In this study, PEG/Cor nanoparticles (PEG/Cor Nps) were prepared by mPEG-DSPE. The PEG/Cor Nps localized in cytoplasm and produced cytotoxicity at high concentration. Whole cell patch clamp examined ion channel functions after incubate PEG/Cor Nps with PC-12 cell. we found that PEG/Cor Nps inhibited voltage-gated Na+ ion channels in a dose- and time-dependent manner but not act on voltage-gated K+ ion channels. The potential mechanisms were revealed by all-atom molecular dynamic (MD) simulations. The results showed that PEG/Cor Nps block the pore of sodium ion channel protein due to dose- and time-dependent accumulation. Besides, the orientation angle (θ) configuration of PEG/Cor Nps will be inverted with the accumulation to generate two blocking mechanisms. Different from other carbon nanomaterials, the blockage mechanism of PEG/Cor Nps provides novel insights into the mechanisms of interaction between carbon nanomaterials and protein.

Decabromodiphenyl ethane affects embryonic development by interfering with nuclear F-actin in zygotes and leads to cognitive and social disorders in offspring mice.

Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 µg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.

Effects of microplastic exposure on the early developmental period and circadian rhythm of zebrafish (Danio rerio): A comparative study of polylactic acid and polyglycolic acid.

Polyglycolic acid (PGA) is an emerging biodegradable plastic material. Together with polylactic acid (PLA), PGA is considered a suitable alternative to conventional plastics and has been widely used in biomedical and food packaging industries. However, degradable plastics continue to face the drawbacks of harsh degradation environment and long degradation time, and may harm the environment and the human body. Therefore, our study focused on assessing the effects of degradable microplastics PGA and PLA on the development and neurobehavior of zebrafish. The results showed that PGA and PLA had little effect on 3-10 hpf embryos. However, developmental stunting was observed in a100 mg/L PGA and PLA-exposed group at 24 hpf. In addition, PGA and PLA exposure decreased the survival and hatching rates, increased wakefulness, and reduced sleep in zebrafish. This indicates that PGA and PLA may affect the circadian behavior of zebrafish by affecting the brain-derived neurotrophic factor (BDNF). Therefore, our results suggest that PGA and PLA exposure induces developmental toxicity, reduces voluntary locomotion, induces of anxiety-like behaviors, and impairs sleep/wake behaviors in zebrafish larvae. This also suggests that the potentially toxic effects of degradable plastics cannot be ignored and that the biological effects of PGA require further research.

Decabromodiphenyl ethane exposure damaged the asymmetric division of mouse oocytes by inhibiting the inactivation of cyclin-dependent kinase 1.

Decabromodiphenyl ethane (DBDPE) is a new brominated flame retardant and is widely added to flammable materials to prevent fire. Because it has been continuously detected in a variety of organisms and humans, it is important to reveal the biological toxicity of DBDPE. However, the influence of DBDPE for female reproduction is unclear. In this study, we investigated whether and how DBDPE exposure affects oocyte development. Female mice as a model were orally exposed to DBDPE by 0, 0.05, 0.5, 5, 50 µg/kg bw/day for 30 days (0.05 µg/kg bw/day is close to the environmental exposure concentration). We found that exposure of mice to DBDPE did not affect the first polar body extrusion (PBE) of oocytes. Strikingly, however, asymmetric division of oocytes was markedly impaired in 5 and 50 µg/kg bw/day DBDPE exposed group, which resulted in oocytes with larger polar bodies (PBs). Then, we further explored and found that DBDPE exposure inhibited the spindle migration and membrane protrusion in oocytes during anaphase of meiosis I (anaphase I), thereby impairing asymmetric division. Additionally, we found that DBDPE exposure suppressed the inactivation of cyclin-dependent kinase 1 (Cdk1), resulting in the decrease of cytoplasmic formin2 (FMN2)-mediated F-actin polymerization in oocytes at the onset of anaphase I. Simultaneously, DBDPE exposure damaged the structural integrity of the spindle and the perpendicular relationship between spindle and cortex. These together led to the failure of spindle migration and membrane protrusion required for oocytes asymmetric division. Finally, DBDPE exposure injured the development of blastocysts, leading to blastocyst apoptosis.

The masculinization steroid milieu caused by fluorene-9-bisphenol disrupts sex-typical courtship behavior in female zebrafish (Danio rerio).

In vertebrates, the behavior of congenital sex differences between males and females is highly dependent on steroid signals and hormonal milieu. The presence of endocrine disrupting chemicals (EDCs) in the environment generally plays a similar role to sex hormones, so its interference with aquatic organism population stability can not be ignored and is worth studying. Fluorene-9-bisphenol (BHPF) has been clarified as an endocrine disruptor on organisms by several studies but its mechanism in perturbation of courtship behavior of female zebrafish is not clear. Here, we proposed an automated multi-zebrafish tracking method quantifying the courtship process and reported that zebrafish females exposed to BHPF, are not receptive to males but rather court females, and lose normal ovarian function with an altered sex steroid milieu. Our results showed that BHPF damaged 17ß-estradiol synthesis by down-regulation of sox3 and cyp19a1a, linking apoptosis with ovary development and female fecundity. The down-regulated expression of estrogen signaling through an estrogen receptor, esr2b, caused the induction of masculinization of female courtship behavior and sexual preference in zebrafish females after BHPF treatment. This process might be mediated by inhibiting the transcription of a neuropeptide B (npb) in the brain. Our study reveals that the estrogen signaling pathway may play an important role in classical courtship behavior and sexual preference of zebrafish. This study provided evidence that anti-estrogenic chemical exposure caused adverse effects on the regulation of the brain-gonad-estrogen axis of aquatic organisms, which should be of concern and highlighted the importance of controlling environmental contamination.

Exposure of zebrafish embryos to sodium propionate disrupts circadian behavior and glucose metabolism-related development.

Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.

Cardiotoxicity of Zebrafish Induced by 6-Benzylaminopurine Exposure and Its Mechanism.

6-BA is a common plant growth regulator, but its safety has not been conclusive. The heart is one of the most important organs of living organisms, and the cardiogenesis process of zebrafish is similar to that of humans. Therefore, based on wild-type and transgenic zebrafish, we explored the development of zebrafish heart under 6-BA exposure and its mechanism. We found that 6-BA affected larval cardiogenesis, inducing defective expression of key genes for cardiac development (myl7, vmhc, and myh6) and AVC differentiation (bmp4, tbx2b, and notch1b), ultimately leading to weakened cardiac function (heart rate, diastolic speed, systolic speed). Acridine orange staining showed that the degree of apoptosis in zebrafish hearts was significantly increased under 6-BA, and the expression of cell-cycle-related genes was also changed. In addition, HPA axis assays revealed abnormally expressed mRNA levels of genes and significantly increased cortisol contents, which was also consistent with the observed anxiety behavior in zebrafish at 3 dpf. Transcriptional abnormalities of pro- and anti-inflammatory factors in immune signaling pathways were also detected in qPCR experiments. Collectively, we found that 6-BA induced cardiotoxicity in zebrafish, which may be related to altered HPA axis activity and the onset of inflammatory responses under 6-BA treatment.

Exposure to melamine cyanuric acid in adult mice induced thyroid dysfunction and circadian rhythm disorder.

MCA is a halogen-free flame retardant. It can cause damage to other tissues such as the kidneys and liver. However, the effects on the circadian rhythm and thyroid in adult mice have not been studied. In this article, adult male mice received MCA at concentrations of 0, 10, 20, 30 mg/kg. The results showed that the time spending on wheel-running and rest bouts changed in different period after MCA exposure. MCA disrupted the T3 and T4 hormone homeostasis and decreased the expression of thyroid hormone synthesis genes. The histological morphology of the thyroid gland was damaged. It was suggested that MCA exposure caused circadian rhythm disorder and thyroid dysfunction.

The toxic effects and possible mechanisms of decabromodiphenyl ethane on mouse oocyte.

Decabromodiphenyl ethane (DBDPE), a widely used new brominated flame retardant, is added into flammable materials to achieve fire retardation. As it is continuously detected in the environment, it has become an emerging environmental pollutant. However, the effects of DBDPE exposure on oocyte maturation and its underlying mechanisms remain unknown. This study found that DBDPE exposure inhibited the rate of germinal vesicle breakdown (GVBD), first polar body extrusion (PBE) and fertilization of mouse oocytes. After 14 h of exposure to DBDPE, metaphase II (MII) oocytes showed that the hardness of zona pellucida (ZP) markedly increased and that the spindle morphology was abnormal. Moreover, DBDPE exposure induced abnormal mitochondrial distribution, mitochondrial dysfunction, and ATP deficiency. Simultaneously, DBDPE exposure down-regulated the expression of antioxidant-related genes (Sod2, Gpx1) and increased the level of reactive oxygen species (ROS) in oocytes. The results of immunofluorescence and qRT-PCR revealed that autophagy occurred in DBDPE-treated oocytes with high expression of autophagy-related protein (LC3) and genes (Lc3, Beclin1). Meanwhile, DBDPE significantly up-regulated the protein (Bax) and mRNA (Bax, Caspase3) levels of pro-apoptosis genes. However, the protein and mRNA expression of anti-apoptosis genes Bcl-2 was dramatically down-regulated in DBDPE-exposed oocytes. Collectively, DBDPE exposure impaired mitochondrial function, causing oxidative damage, autophagy and apoptosis in oocytes.

Melatonin mitigated circadian disruption and cardiovascular toxicity caused by 6-benzylaminopurine exposure in zebrafish.

As a highly effective plant hormone, the overuse of 6-benzylaminopurine (6-BA) may pose potential threats to organisms and the environment. Melatonin is widely known for its regulation of sleep rhythm, and it also shows a beneficial effect in a variety of adverse situations. In order to investigate the harm of 6-BA to vertebrates and whether melatonin can reverse the toxicity induced by 6-BA, we analyzed the circadian rhythm and cardiovascular system of zebrafish, and further clarified the role of the thyroid endocrine system. The exposure of well-developed embryos started at 2 hpf, then 6-BA and/or melatonin were carried out. The results indicated that 6-BA disturbed the rhythmic activities of the larvae, increased wakefulness, correspondingly reduced their rest, and induced disrupted clock gene expression. Video analysis and qRT-PCR data found that zebrafish under 6-BA exposure showed obvious cardiovascular morphological abnormalities and dysfunction, and the mRNA levels of cardiovascular-related genes (nkx2.5, gata4, myl7, vegfaa and vegfab) were significantly down-regulated. In addition, altered thyroid hormone content and hypothalamus-pituitary-thyroid (HPT) axis-related gene expression were also clearly observed. 1umol/L of melatonin had little effect on zebrafish, but its addition could significantly alleviate the circadian disturbance and cardiovascular toxicity caused by 6-BA, and simultaneously played a regulatory role in thyroid system. Our research revealed the adverse effects of 6-BA on zebrafish larvae and the protective role of melatonin in circadian rhythm, cardiovascular and thyroid systems.

Exposure to Melamine cyanuric acid in adolescent mice caused emotional disorder and behavioral disorder.

Melamine cyanuric acid (MCA) is a flame retardant linked by hydrogen bonds between melamine and cyanuric acid. MCA is used in an excellent series of phosphorus and nitrogen flame retardants. MCA can harm the kidney, liver, testis, and spleen cells. However, the effects of MCA on the emotions and behaviour of adolescent mice have not yet been investigated. In this article, male mice were exposed to MCA at 10, 20, and 40 mg/kg for four weeks. MCA exposure resulted in enhanced mouse locomotor and nocturnal activity. We also observed anxiety-like and depression-like behaviours. Moreover, after MCA exposure, the serum concentrations of thyroid-related hormones were changed, and the mRNA levels were affected. In short, MCA exposure can cause behavioural and emotion disorders.

Acute fluorene-9-bisphenol exposure damages early development and induces cardiotoxicity in zebrafish (Danio rerio).

Fluorene-9-bisphenol (BHPF) is a substitute for bisphenol A (BPA), which is widely used to manufacture plastic products. Previous studies indicate that BHPF has an anti-estrogenic effect and induces cytotoxicity in mice oocytes. However, the effects of acute BHPF exposure on the aquatic organism obtain little attention. In this study, a series of BHPF concentrations (1 µM, 2 µM, 5 µM, 10 µM, 20 µM) was used to exposed zebrafish embryos from 2 h post-fertilization (hpf). The results showed the LC50 at 96hpf was 2.88 µM (1.01 mg/L). Acute exposure induced malformation in morphology, and retarded epiboly rate at 10hpf, increased apoptosis. Moreover, acute BHPF exposure led cardiotoxicity, by impeding cardiac looping, decreasing cardiac contractility (reducing the stroke volume and cardiac output, decreasing fractional shortening of ventricle). Besides that, BHPF exposure altered the expression of cardiac transcriptional regulators and development related genes. In conclusion, acute BHPF exposure induced developmental abnormality, retarded cardiac morphogenesis and injured the cardiac contractility. This study indicated BHPF would be an unneglected threat for the safety of aquatic organisms.

Joint effect of surfactants and cephalexin on the formation of Escherichia coli filament.

Both antibiotics and surfactants commonly exist in natural environment and have generated great concerns due to their biological influence on the ecosystem. A major concern lies in the capacity of antibiotics to induce bacterial filaments formation, which has potential health risks. However, their joint effect is not clear so far. Here, we studied the joint effect of cephalexin (Cex), a typical antibiotic, and differently charged surfactants on the formation of E. coli filaments. Three kinds of surfactants characterized by different charges were used: cationic surfactant (CTAB), anionic surfactant (SDS) and nonionic surfactant (Tween). Data showed that Cex alone caused the formation of E. coli filaments, elongating their maximum profile from ca. 2 µm (a single E. coli cell) to tens of micrometers (an E. coli filament). A joint use of surfactants with Cex could produce even longer E. coli filaments, elongating the maximum length of the bacteria to larger than 100 µm. The capacity order of different surfactants under their optimum concentrations to produce elongated E. coli filaments was Tween > SDS > CTAB. The E. coli filaments were characterized with a normal DNA distribution and a good cell membrane integrity. We measured the stiffness of bacterial cell wall by atomic force microscopy and correlated the elongation capacity of the E. coli filaments to the stiffness of cell wall. Zeta potential measurement indicated that inserting into or being bound to the cell surface in a large quantity was tested not to be the major way that surfactants interacted with bacteria.

Melatonin protects embryonic development and maintains sleep/wake behaviors from the deleterious effects of fluorene-9-bisphenol in zebrafish (Danio rerio).

Environmental endocrine chemicals have various adverse effects on the development of vertebrates. Fluorene-9-bisphenol (BHPF), a substitute of bisphenol A (BPA), is widely used in commercial production. The effects of BHPF on development and behavior are unclear. Melatonin plays a protective role under many unfavorable conditions. In this study, we investigated the effects of BHPF on the development and behaviors of zebrafish and whether melatonin reverses effects induced by BHPF. Zebrafish embryos were exposed to 0.1, 10, or 1000 nmol/L BHPF with or without 1 µmol/L melatonin from 2 hours postfertilization to 6 days postfertilization. The results showed that 0.1 and 10 nmol/L BHPF had little effect on development. High-dose BHPF (1000 nmol/L) delayed the development, increased mortality and surface tension of embryonic chorions, caused aberrant expression of the key genes (ntl, shh, krox20, pax2, cmlc2) in early development detected by in situ hybridization, and damaged the CaP motor neurons, which were associated with locomotion ability detected by immunofluorescence. Melatonin addition reversed or weakened these adverse effects of BHPF on development, and melatonin alone increased surface tension as the effects of high-dose BHPF. However, all groups of BHPF exposure triggered insomnia-like behaviors, with increased waking activity and decreased rest behaviors. BHPF acted on the hypocretin (hcrt) system and upregulated the expression of sleep/wake regulators such as hcrt, hcrt receptor (hcrtr), arylalkylamine N-acetyltransferase-2 (aanat2). Melatonin recovered the alternation of sleep/wake behaviors induced by BHPF and restored abnormal gene expression to normal levels. This study showed that high-dose BHPF had adverse effects on early development and induced behavioral alternations. However, melatonin prevented BHPF-induced aberrant development and sleep/wake behaviors.

Fluorene-9-bisphenol exposure induces cytotoxicity in mouse oocytes and causes ovarian damage.

Fluorene-9-bisphenol (BHPF), a substitute for bisphenol A, is a chemical component of plastics for industrial production. There is evidence that BHPF exerts an antioestrogenic effect on mice, induces endometrial atrophy and leads to adverse pregnancy outcomes. However, the effects of BHPF on oocyte maturation and ovary development as well as its possible mechanisms remain unclear. The objective of this study was to investigate the toxicity and mechanism of BHPF exposure in mouse oocytes in vitro and in vivo. Our results showed that BHPF could inhibit the maturation of oocytes in vitro by reducing the protein level of p-MAPK and destroying the meiotic spindle. We found that in vitro, BHPF-treated oocytes showed increased ROS levels, DNA damage, mitochondrial dysfunction, and expression of apoptosis- and autophagy-related genes, such as Bax, cleaved-caspase 3, LC 3 and Atg 12. In addition, in vivo experiments showed that BHPF exposure could induce the expression of oxidative stress genes (Cat, Gpx 3 and Sod 2) and apoptosis genes (Bax, Bcl-2 and Cleaved-caspase 3) and increase the number of atresia follicles in the ovaries. Our data showed that BHPF exposure affected the first polar body extrusion of oocytes, increased oxidative stress, destroyed spindle assembly, caused DNA damage, altered mitochondrial membrane potentials, induced apoptosis and autophagy, and affected ovarian development.

Reversal of reserpine-induced depression and cognitive disorder in zebrafish by sertraline and Traditional Chinese Medicine (TCM).

BACKGROUND: With increased social pressure, individuals face a high risk of depression. Subsequently, depression affects cognitive behaviour and negatively impacts daily life. Fortunately, the Traditional Chinese Medicine Jia Wei Xiao Yao (JWXY) capsule is effective in reducing depression and improving cognitive behaviour. METHODS: The constituents of JWXY capsule were identified by ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry analyses. We analysed behaviours of depression-like zebrafish in the novel tank with an automatic 3D video-tracking system and conducted the colour preference test, as well detected physiological changes after sertraline and JWXY capsule treatments. RESULTS: Both sertraline and JWXY capsule rescued the decreased locomotive behaviour and depression phenotype of zebrafish caused by reserpine. JWXY capsule especially improved the inhibited exploratory behaviour caused by reserpine. In addition, with the onset of depressive behaviour, zebrafish exhibited alterations in cognitive behaviour as indicated by colour preference changes. However, compared with sertraline, JWXY capsule was more efficaciously in rescuing this change in the colour preference pattern. Moreover, an increased level of cortisol, increased expression of tyrosine hydroxylase (TH) and decreased monoamine neurotransmitters, including serotonin (5-HT) and noradrenaline, were involved in the depressive behaviours. In addition, sertraline and JWXY capsule rescued the depressive phenotype and cognitive behaviour of zebrafish by altering the levels of endogenous cortisol and monoamine neurotransmitters. CONCLUSIONS: JWXY capsule was more effectively than sertraline in rescuing reserpine-induced depression and cognitive disorder in zebrafish. Potentially, our study can provide new insights into the clinical treatment of depression and the mechanism of action of JWXY capsule.

Puerarin and Amlodipine Improvement of D-Galactose-Induced Impairments of Behaviour and Neurogenesis in Mouse Dentate Gyrus: Correlation with Glucocorticoid Receptor Expression.

Glucocorticoid receptors (GRs) exert actions on the hippocampus that are important for memory formation. There are correlations between vascular dysfunctions and GR-related gene expression. Both vascular dysfunction and GR gene expression decline occur during the ageing process. Therefore, hypotensors, which have effects on improving vascular dysfunction, may be able to ameliorate GR gene expression decline in ageing mice and improve ageing-mediated memory deficits. In this study, we hypothesized that hypotensors could alleviate the decline of GR gene expression and ameliorate age-induced learning and memory deficits in a D-gal-induced ageing mice model. In line with our hypothesis, we found that chronic D-gal treatment decreased GR and DCX expression in the hippocampus, leading to learning and memory deficits. Amlodipine (AM) and puerarin (PU) treatment improved GR gene expression decline in the hippocampus and ameliorated the learning and memory deficits of D-gal-treated mice. These changes correlated with enhanced DCX expression and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, PU treatment conveyed better effects than AM treatment, but combination therapy did not enhance the effects on improving GR expression. However, we did not find evidence of these changes in non-D-gal-treated mice that lacked GR gene expression decline. These results suggest that AM and PU could improve D-gal-induced behavioural deficits in correlation with GR gene expression.