Developmental and Neurotoxicity of Acrylamide to Zebrafish

Acrylamide is a commonly used industrial chemical that is known to be neurotoxic to mammals. However, its developmental toxicity is rarely assessed in mammalian models because of the cost and complexity involved. We used zebrafish to assess the neurotoxicity, developmental and behavioral toxicity of acrylamide. At 6 h post fertilization, zebrafish embryos were exposed to four concentrations of acrylamide (10, 30, 100, or 300 mg/L) in a medium for 114 h. Acrylamide caused developmental toxicity characterized by yolk retention, scoliosis, swim bladder deficiency, and curvature of the body. Acrylamide also impaired locomotor activity, which was measured as swimming speed and distance traveled. In addition, treatment with 100 mg/L acrylamide shortened the width of the brain and spinal cord, indicating neuronal toxicity. In summary, acrylamide induces developmental toxicity and neurotoxicity in zebrafish. This can be used to study acrylamide neurotoxicity in a rapid and cost-efficient manner.     

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

The mechanisms of resistance to antidepressant drugs is a key and still unresolved problem of psychopharmacology. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play a key role in the therapeutic effect of many antidepressants. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT synthesis in the brain. We used zebrafish (Danio rerio) as a promising model organism in order to elucidate the effect of TPH2 deficiency caused by p-chlorophenylalanine (pCPA) on the alterations in behavior and expression of 5-HT-related (Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa) and BDNF-related (Creb, Bdnf, Ntrk2a, Ngfra) genes in the brain after prolonged treatment with two antidepressants, inhibitors of 5-HT reuptake (fluoxetine) and oxidation (pargyline). In one experiment, zebrafish were treated for 72 h with 0.2 mg/L fluoxetine, 2 mg/L pCPA, or the drugs combination. In another experiment, zebrafish were treated for 72 h with 0.5 mg/L pargyline, 2 mg/L pCPA, or the drugs combination. Behavior was studied in the novel tank diving test, mRNA levels were assayed by qPCR, 5-HT and its metabolite concentrations were measured by HPLC. The effects of interaction between pCPA and the drugs on zebrafish behavior were observed: pCPA attenuated “surface dwelling” induced by the drugs. Fluoxetine decreased mRNA levels of Tph2 and Htr2aa genes, while pargyline decreased mRNA levels of Slc6a4b and Htr1aa genes. Pargyline reduced Creb, Bdnf and Ntrk2a genes mRNA concentration only in the zebrafish treated with pCPA. The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.     

金纳米颗粒的自组装修饰及其生物学效应

为了探究金纳米颗粒(Au NP)s的表面自组装亲疏水性修饰及其生物学效应,通过自组装技术制备SH-(CH2)11OH和SH-(CH2)11CH3不同配比修饰的Au NPs,并用透射电子显微镜(TEM)、纳米粒度仪和傅里叶变换红外光谱(FT-IR)检测修饰后的表面形貌与结构特征。用体视显微镜观察Au NPs修饰后对斑马鱼胚胎/幼鱼表型的影响。用MMT、NO含量试剂盒、总抗氧化能力(T-AOC)试剂盒检测Au NPs修饰后对人脐静脉内皮细胞(HUVECs)毒性和功能指标的影响。利用电感耦合等离子体发射光谱和TEM检测Au NPs修饰后被HUVECs摄入情况。结果表明,用SH-(CH2)11OH修饰比用SH-(CH2)11CH3修饰的Au NPs毒性大,当修饰Au NPs的SH-(CH2)11OH和SH-(CH2)11CH3配比为50:50时毒性最小。     

Neurotrophins Time Point Intervention after Traumatic Brain Injury: From Zebrafish to Human

Traumatic brain injury (TBI) remains the leading cause of long-term disability, which annually involves millions of individuals. Several studies on mammals reported that neurotrophins could play a significant role in both protection and recovery of function following neurodegenerative diseases such as stroke and TBI. This protective role of neurotrophins after an event of TBI has also been reported in the zebrafish model. Nevertheless, reparative mechanisms in mammalian brain are limited, and newly formed neurons do not survive for a long time. In contrast, the brain of adult fish has high regenerative properties after brain injury. The evident differences in regenerative properties between mammalian and fish brain have been ascribed to remarkable different adult neurogenesis processes. However, it is not clear if the specific role and time point contribution of each neurotrophin and receptor after TBI is conserved during vertebrate evolution. Therefore, in this review, I reported the specific role and time point of intervention for each neurotrophic factor and receptor after an event of TBI in zebrafish and mammals.     

A jump persistent turning walker to model zebrafish locomotion

Zebrafish are gaining momentum as a laboratory animal species for the investigation of several functional and dysfunctional biological processes. Mathematical models of zebrafish behaviour are expected to considerably aid in the design of hypothesis-driven studies by enabling preliminary in silico tests that can be used to infer possible experimental outcomes without the use of zebrafish. This study is motivated by observations of sudden, drastic changes in zebrafish locomotion in the form of large deviations in turn rate. We demonstrate that such deviations can be captured through a stochastic mean reverting jump diffusion model, a process that is commonly used in financial engineering to describe large changes in the price of an asset. The jump process-based model is validated on trajectory data of adult subjects swimming in a shallow circular tank obtained from an overhead camera. Through statistical comparison of the empirical distribution of the turn rate against theoretical predictions, we demonstrate the feasibility of describing zebrafish as a jump persistent turning walker. The critical role of the jump term is assessed through comparison with a simplified mean reversion diffusion model, which does not allow for describing the heavy-tailed distributions observed in the fish turn rate.     

基因突变斑马鱼骨纳米力学性能的改变

在基因突变的dml型斑马鱼中第一次发现纳米力学性能的明显改变.与野生型斑马鱼骨相比,基因突变的dml型斑马鱼的蚋米压痕的硬度和弹性模量均大大降低.断裂表面的SEM形貌照片进一步揭示了在基因突变的鱼骨中,正常骨的夹板状结构不再存在,形成的微裂纹使力学性能减小,与正常鱼相比,骨的脆性明显增加.     

Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity

In this study, we used the zebrafish animal model to establish a bioassay by which physiological efficacy differential of alpha-melanocyte-stimulating hormone (α-MSH) analogues could be measured by melanosome dispersion in zebrafish larvae. Brain-skin connection research has purported the interconnectedness between the nervous system and skin physiology. Accordingly, the neuropeptide α-MSH is a key regulator in several physiological processes, such as skin pigmentation in fish. In mammals, α-MSH has been found to regulate motivated behavior, appetite, and emotion, including stimulation of satiety and anxiety. Several clinical and animal model studies of autism spectrum disorder (ASD) have already demonstrated the effectiveness of α-MSH in restoring the social deficits of autism. Therefore, we sought to analyze the effect of synthetic and naturally-occurring α-MSH variants amongst different species. Our results showed that unique α-MSH derivatives from several fish species produced differential effects on the degree of melanophore dispersion. Using α-MSH human form as a standard, we could identify derivatives that induced greater physiological effects; particularly, the synthetic analogue melanotan-II (MT-II) exhibited a higher capacity for melanophore dispersion than human α-MSH. This was consistent with previous findings in an ASD mouse model demonstrating the effectiveness of MT-II in improving ASD behavioral symptoms. Thus, the melanophore assay may serve as a useful screening tool for therapeutic candidates for novel drug discovery.     

How body torque and Strouhal number change with swimming speed and developmental stage in larval zebrafish

Small undulatory swimmers such as larval zebrafish experience both inertial and viscous forces, the relative importance of which is indicated by the Reynolds number (Re). Re is proportional to swimming speed (v_swim) and body length; faster swimming reduces the relative effect of viscous forces. Compared with adults, larval fish experience relatively high (mainly viscous) drag during cyclic swimming. To enhance thrust to an equally high level, they must employ a high product of tail-beat frequency and (peak-to-peak) amplitude fA_tail, resulting in a relatively high fA_tail/v_swim ratio (Strouhal number, St), and implying relatively high lateral momentum shedding and low propulsive efficiency. Using kinematic and inverse-dynamics analyses, we studied cyclic swimming of larval zebrafish aged 2–5 days post-fertilization (dpf). Larvae at 4–5 dpf reach higher f (95 Hz) and A_tail (2.4 mm) than at 2 dpf (80 Hz, 1.8 mm), increasing swimming speed and Re, indicating increasing muscle powers. As Re increases (60 → 1400), St (2.5 → 0.72) decreases nonlinearly towards values of large swimmers (0.2–0.6), indicating increased propulsive efficiency with v_swim and age. Swimming at high St is associated with high-amplitude body torques and rotations. Low propulsive efficiencies and large yawing amplitudes are unavoidable physical constraints for small undulatory swimmers.     

Repelled from the wound,or randomly dispersed? Reverse migration behaviour of neutrophils characterized by dynamic modelling

Following neutralization of infectious threats, neutrophils must be removed from inflammatory sites for normal tissue function to be restored. Recently, a new paradigm has emerged, in which viable neutrophils migrate away from inflammatory sites by a process best described as reverse migration. It has generally been assumed that this process is the mirror image of chemotaxis, where neutrophils are drawn into the areas of infection or tissue damage by gradients of chemotactic cues. Indeed, efforts are underway to identify cues that drive neutrophils away by the reverse process, fugetaxis. By using photoconvertible pigments expressed in neutrophils in transparent zebrafish larvae, we were able to image the position of each neutrophil during inflammation resolution in vivo. These neutrophil coordinates were analysed within a dynamic modelling framework, using different forms of the drift–diffusion equation with model selection and parameter estimation based on approximate Bayesian computation. This analysis revealed the experimental data were best fitted by a model incorporating a diffusion term but no drift term—where the presence of drift would indicate fugetaxis. This result, for the first time, provides rigorous data-driven evidence that reverse migration of neutrophils in vivo is not a form of fugetaxis, but rather a stochastic redistribution.