Search

The creatine kinase system is crucial for maintaining cellular energy homeostasis and plays a role in regulating locomotor behavior in organisms, but its significance in the regulating the motionless behavior in olive flounder is limited. In the first experiment of this study, elevated levels of creatine kinase (CK) activity in the spinal cord were detected in the juvenile group (JG) flounder compared to the adult group (AG) flounder. In the second experiment, to further confirm the involvement of CK in the locomotor behavior, the adult flounder was given an intraperitoneal injection of creatine (150 mg/kg), while the flounder in the control group received a saline solution. After one week post-injection, the behavioral analysis revealed that the flounder in the creatine-treated group displayed higher levels of locomotor activity and a greater number of escape attempts in response to external stimuli when compared to the control group. However, the acute stress response, induced by intraperitoneal injection and characterized by tail beating, was significantly alleviated in the flounder in the creatine-treated group. Additionally, there was an upregulation of the UII and AchR genes in the spinal cord, as well as increased levels of UII and AchR in the muscle tissues of the creatine-treated flounder. However, a reduction in UI mRNA levels was observed in the brain of the flounder. Collectively, our data provide the evidence that the elevated enzyme activity and gene expression of creatine kinase play important roles in off-bottom swimming behavior in the JG flounder. Furthermore, administration of creatine improved the locomotor activity and alleviated the stress response in flounder, which is associated with regulation of the locomotor- and stress-related gene in the brain, spinal cord, and muscle. [Display omitted] • High levels of creatine kinase activity were detected in the spinal cord of JG flounder. • Creatine-treated flounder displayed a higher locomotor activity and less struggling behavior. • U-II and PA in spinal cord, AchR and UTR in muscle were up-regulated in the creatine-treated flounder. • UI and slc6a8 mRNA in brain was significantly decreased in the creatine-treated flounder. [ABSTRACT FROM AUTHOR]

Isopropylate Triphenyl Phosphate (IPPP), a novel organophosphorus flame retardant, has become a widespread environmental pollutant. However, the toxic effects and mechanisms of IPPP remain unclear. In this study, we evaluated the neurodevelopmental toxicity effects of IPPP on zebrafish embryonic development, neurobehavior, and physiological and transcriptomic changes. The results showed that IPPP induced adverse developments such as low survival rates and hatching rates, decreased body length and eye distance, and also led to increased heart rates and embryonic malformation rates. The developmental defects mainly included typical pericardial edema, eye deformities, and a reduction in the number of newborn neurons. Mitochondrial energy metabolism disorders and apoptosis of cardiomyocytes may be responsible for heart malformation. Behavioral results showed that IPPP caused abnormal changes in swimming speed, total swimming distance and trajectory, and showed a low-dose effect. In addition, the decreased activity of neurotransmitters such as acetylcholinesterase (AchE) and dopamine (DA), and the changes in genes related to the central nervous system (CNS) and metabolism pathway may be the causes of neurodevelopmental toxicity of IPPP. Meanwhile, IPPP induced oxidative stress and apoptosis, and changed the ATPase activity of zebrafish larvae by altering nuclear factor erythroid2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing results indicated that Cytochrome P450 and drug metabolism, Energy metabolism-related pathways, Glutathione metabolism, Retinoid acid (RA) and REDOX signaling pathways were significantly enriched, and most of the genes in these pathways were up-regulated after IPPP treatment, which may be new targets for IPPP-induced neurodevelopment. In summary, the results of this study provide an important reference for a comprehensive assessment of the toxic effects and health risks of the new pollutant IPPP. [Display omitted] • Neurodevelopmental and heart defects may serve as plausible target organ for IPPP exposure. • IPPP triggered oxidative stress, apoptosis and activated the Nrf2-ARE signaling pathway. • Energy metabolism-related pathways participate in the toxicity of IPPP. • Cytochrome P450, Glutathione metabolism, Retinoid acid (RA) signaling pathways may be novel targets of IPPP exposure. • Abnormal behaviors contributed by co-regulation of neurotransmitters, energy metabolism, oxidative stress, and visual perception. [ABSTRACT FROM AUTHOR]

Microplastics/nanoplastics (MNPs) inevitably coexist with other pollutants in the natural environment, making it crucial to study the interactions between MNPs and other pollutants as well as their combined toxic effects. In this study, we investigated neurotoxicity in marine medaka (Oryzias melastigma) exposed to polystyrene micro/nanoplastics (PS-MNPs), triphenyltin (TPT), and PS-MNPs + TPT from physiological, behavioral, biochemical, and genetic perspectives. The results showed that marine medaka exposed to 200 ng/L TPT or 200 μg/L PS-NPs alone exhibited some degree of neurodevelopmental deficit, albeit with no significant behavioral abnormalities observed. However, in the PS-MP single exposure group, the average acceleration of short-term behavioral indices was significantly increased by 78.81%, indicating a highly stress-responsive locomotor pattern exhibited by marine medaka. After exposure to PS-MNPs + TPT, the swimming ability of marine medaka significantly decreased. In addition, PS-MNPs + TPT exposure disrupted normal neural excitability as well as activated detoxification processes in marine medaka larvae. Notably, changes in neural-related genes suggested that combined exposure to PS-MNPs and TPT significantly increased the neurotoxic effects observed with exposure to PS-MNPs or TPT alone. Furthermore, compared to the PS-MPs + TPT group, PS-NPs + TPT significantly inhibited swimming behavior and thus exacerbated the neurotoxicity. Interestingly, the neurotoxicity of PS-MPs was more pronounced than that of PS-NPs in the exposure group alone. However, the addition of TPT significantly enhanced the neurotoxicity of PS-NPs compared to PS-MPs + TPT. Overall, the study underscores the combined neurotoxic effects of MNPs and TPT, providing in-depth insights into the ecotoxicological implications of MNPs coexisting with pollutants and furnishing comprehensive data. [Display omitted] • PS-NP exposure induces neurotoxicity but does not alter behavior. • PS-MP exposure enhances short-term neuroexcitability in marine medaka. • Combined exposure to PS-MNPs and TPT causes nerve damage that impairs locomotor performance. • PS-NPs amplifies TPT-induced neurotoxicity more than PS-MPs. [ABSTRACT FROM AUTHOR]

• A large cage stimulates a physically active lifestyle in mice. • Trained mice kept in a large cage exhibited high OXR1 in hypothalamus and liver. • A more active lifestyle provides a protective effect against oxidative damage. • An up-regulation of OXR1 may be induced by changes in energy metabolism. • SPA in the context of antioxidant defense should be further explored. Oxidation resistance protein 1 (OXR1) is of scientific interest due its role in protecting tissues against oxidative stress, DNA mutations and tumorigenesis, but little is known regarding strategies to increase OXR1 in different tissues. As an improved antioxidant defense may result from a high total amount of physical activity, the present study was designed to determine whether an active lifestyle including aerobic training exercise and spontaneous physical activity (SPA) can increase OXR1. We have built a large cage (LC) that allows animals to move freely, promoting an increase in SPA in comparison to a small cage (SC). We examined the effects of aerobic training applied for 8 weeks on SPA and OXR1 of C57BL/6 J mice living in two types of housing (SC and LC). OXR1 protein was studied in hypothalamus, muscle and liver, which were chosen due to their important role in energy and metabolic homeostasis. LC-mice were more active than SC-mice as determined by SPA values. Despite both trained groups exhibiting similar gains in aerobic capacity, only trained mice kept in a large cage (but not for trained mice housed in SC) exhibited high OXR1 in the hypothalamus and liver. Trained mice housed in LC that exhibited an up-regulation of OXR1 also were those who exhibited an energy-expensive metabolism (based on metabolic parameters). These results suggest that aerobic training associated with a more active lifestyle exerts a protective effect against oxidative damage and may be induced by changes in energy metabolism. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) is a herbicide widely used in agriculture to control weeds. The damage caused to health through intoxication requires studies to combating its damage to health. Bougainvillea glabra Choisy is a plant native to South America and its bracts contain a variety of compounds, including betalains and phenolic compounds, which have been underexplored about their potential applications and benefits for biological studies to neutralize toxicity. In this study, we evaluated the antioxidant and protective potential of the B. glabra bracts (BBGCE) hydroalcoholic extract against Paraquat-induced toxicity in Drosophila melanogaster. BBGCE demonstrated high antioxidant capacity in vitro through the assays of ferric-reducing antioxidant power (FRAP), radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), free radical ABTS and quantification of phenolic compounds, confirmed through identifying the main compounds. Wild males of D. melanogaster were exposed to Paraquat (1.75 mM) and B. glabra Choisy (1, 10, 50 and 100 μg/mL) in agar medium for 4 days. Flies exposed to Paraquat showed a reduction in survival rate and a significant decrease in climbing capacity and balance test when compared to the control group. Exposure of the flies to Paraquat caused a reduction in acetylcholinesterase activity, an increase in lipid peroxidation and production of reactive species, and a change in the activity of the antioxidant enzymes. Co-exposure with BBGCE was able to block toxicity induced by PQ exposure. Our results demonstrate that bract extract has a protective effect against PQ on the head and body of flies, attenuating behavioral deficit, exerting antioxidant effects and blocking oxidative damage in D. melanogaster. [Display omitted] • Antioxidant and protective potential of the extract of Bougainvillea glabra bract extract were evaluated. • Flies exposed to Paraquat showed a reduction in survival rate when compared to the control group. • Bougainvillea glabra bract extract decreases the production of reactive species. • Bougainvillea glabra bract extract shows a protective effect against the Paraquat. [ABSTRACT FROM AUTHOR]

Triphenyl phosphate (TPhP) is a widely used organophosphorus flame retardant, which has become ubiquitous in the environment. However, little information is available regarding its transgenerational effects. This study aimed to investigate the developmental toxicity of TPhP on F1 larvae offspring of adult male zebrafish exposed to various concentrations of TPhP for 28 or 60 days. The findings revealed significant morphological changes, alterations in locomotor behavior, variations in neurotransmitter, histopathological changes, oxidative stress levels, and disruption of Retinoic Acid (RA) signaling in the F1 larvae. After 28 and 60 days of TPhP exposure, the F1 larvae exhibited a myopia-like phenotype with pathological alterations in the lens and retina. The genes involved in the RA signaling pathway were down-regulated following parental TPhP exposure. Swimming speed and total distance of F1 larvae were significantly reduced by TPhP exposure, and long-term exposure to environmental levels of TPhP had more pronounced effects on locomotor behavior and neurotransmitter levels. In conclusion, TPhP induced histological and morphological alterations in the eyes of F1 larvae, leading to visual dysfunction, disruption of RA signaling and neurotransmitter systems, and ultimately resulting in neurobehavioral abnormalities. These findings highlight the importance of considering the impact of TPhP on the survival and population reproduction of wild larvae. [Display omitted] • Parental TPhP exposure triggered developmental toxicity and abnormal behaviors in F1 larvae. • Parental TPhP exposure induced significant eye development disorders in F1 larvae. • Abnormal behaviors contributed by co-regulation of visual dysfunction and neurotransmitter imbalances. • The RA signaling pathway involved in eye development exhibited significant changes. [ABSTRACT FROM AUTHOR]

This study evaluated the reactive biomechanical strategies associated with both upper- and lower-body (lead and trail limbs) following the first exposures to (un)expected stepdown at comfortable (1.22 ± 0.08 m/s) and fast (1.71 ± 0.11 m/s) walking velocities. Eleven healthy adults completed 34 trails per walking velocity over an 8-m, custom-built track with two forceplates embedded in its center. For the expected stepdown, the track was lowered by 0-, −10- and −20-cm from the site of the second forceplate, whereas the unexpected stepdown was created by camouflaging the second forceplate (−10-cm). Two-way repeated-measurement ANOVAs detected no velocity-related effects of stepdown on kinematic and kinetic parameters during lead limb stance-phase, and on the trail limb stepping kinematics. However, analyses of significant interactions revealed greater peak flexion angles across the trunk and the trail limb joints (hip, knee and ankle) in unexpected versus expected stepdown conditions at a faster walking velocity. The −10-cm unexpected stepdown (main effect) had a greater influence on locomotor behavior compared to expected conditions due mainly to the absence of predictive adjustments, reflected by a significant decrease in peak knee flexion, contact time and vertical impulse during stance-phase. Walking faster (main effect) was associated with an increase in hip peak flexion and net anteroposterior impulse, and a decrease in contact time and vertical impulse during stepdown. The trail limb, in response, swung forward faster, generating a larger and faster recovery step. However, such reactive stepping following unexpected stepdown was yet a sparse compensation for an unstable body configuration, assessed by significantly smaller step width and anteroposterior margin-of-stability at foot-contact in the first-recovery-step compared with expected conditions. These findings depict the impact of the expectedness of stepdown onset on modulation of global dynamic postural control for a successful accommodation of (un)expected surface elevation changes in young, healthy adults. [ABSTRACT FROM AUTHOR]

Abstract As an alternate of bisphenol A (BPA), bisphenol S (BPS) is now widely used to produce our daily consumer goods. Some studies have shown that BPS has the potential to disrupt the reproduction and glucose homeostasis. However, the impact of BPS on the nervous system remains unclear. The purpose of this study is to investigate the impact of BPS on the nervous systems of zebrafish in their early growing stages. The 96 h-LC 50 value of BPS to zebrafish larvae was 323 mg/L (95%CI: 308–339 mg/L). Zebrafish embryos were exposed to BPS at concentrations of 0, 0.03, 0.3 and 3.0 mg/L until 6 days postfertilization. Our results showed that 0.3 and 3.0 mg/L BPS exposure markedly decreased locomotor behavior, accompany by the increased oxidative stress, promoted apoptosis and altered retinal structure in zebrafish. In addition, the expression levels of six neurodevelopment genes (α1-tubuli n, elavl3 , gap43 , mbp , syn2a and gfap) were downregulated after 3.0 mg/L BPS treatment. In conclusion, BPS may affect locomotor behavior and alter retinal structure in zebrafish larvae partially by increasing oxidative stress, and by suppressing the expression levels of neurodevelopment genes. Graphical abstract Image Highlights • The developmental neurotoxicity of bisphenol S in zebrafish. • Bisphenol S exposure markedly decreased locomotor behavior. • Bisphenol S exposure promoted apoptosis and altered retinal structure in zebrafish. • Bisphenol S exposure downregulate the expression levels of neurodevelopment genes. [ABSTRACT FROM AUTHOR]

Abstract Under stressful conditions, cellular heme catabolism to carbon monoxide, iron and biliverdin is mediated by the 32 kDa enzyme, heme oxygenase-1 (HO-1). A wide range of pro-oxidant and inflammatory stimuli act on diverse consensus sequences within the Hmox1 promoter to rapidly induce the gene. There is ample evidence attesting to the beneficial effects of HO-1 upregulation in brain. By converting pro-oxidant heme to the antioxidants, biliverdin and bilirubin, HO-1/biliverdin reductase may help restore a more favorable tissue redox microenvironment. Contrariwise, in some cell types and under certain circumstances, heme-derived carbon monoxide and iron may amplify intracellular oxidative stress and exacerbate the disease process. This inimical side of neural HO-1 has often been ignored in biomedical literature promulgating interventions aimed at boosting central HO-1 expression for the management of diverse CNS conditions and is the focus of the current review. A comprehensive model of astroglial stress is presented wherein sustained Hmox1 induction promotes oxidative mitochondrial membrane damage, iron sequestration and mitophagy (macroautophagy). The HO-1 mediated gliopathy renders nearby neuronal constituents vulnerable to oxidative injury and recapitulates 'core' neuropathological features of many aging-related neurodegenerative and some neurodevelopmental brain disorders. A balanced literature should acknowledge that, in a host of chronic human CNS afflictions, the glial HO-1 response may serve as a robust transducer of noxious stimuli, an important driver of relevant neuropathology and a potentially disease-modifying therapeutic target. [ABSTRACT FROM AUTHOR]

Highlights • MeHg + MSG diet reduced total thiol levels in the experimental cockroaches. • TBARS level increased in cockroaches exposed to diet containing MeHg + MSG. • MeHg + MSG diet disrupted locomotor and behavioral parameters in cockroaches. • GST activity was not significantly altered in cockroaches exposed to MeHg + MSG diet. • MeHg + MSG cockroaches decreased the acetylcholinesterase activity. Abstract The present study aims to investigate the effect of monosodium glutamate (MSG) both separately and combined with a low dose of methylmercury (MeHg) on behavioral and biochemical parameters in Nauphoeta cinerea (lobster cockroach). Cockroaches were fed with the basal diet alone, basal diet + 2% NaCl, basal diet + 2% MSG; basal diet + 0.125 mg/g MeHg, basal diet + 0.125 mg/g MeHg + 2% NaCl; and basal diet + 0.125 mg/g MeHg + 2% MSG for 21 days. Behavioral parameters such as distance traveled, immobility and turn angle were automatically measured using ANY-maze video tracking software (Stoelting, CO, USA). Biochemical end-points such as acetylcholinesterase (AChE), glutathione- S -transferase (GST), total thiol and TBARS were also evaluated. Results show that MeHg + NaCl, increased distance traveled while MeHg + MSG increased time immobile. AChE activity was significantly reduced in cockroaches across all the groups when compared to the control. There was no significant alteration in GST activity and total thiol levels. It could be that both NaCl and MSG potentiates the neurotoxic effect of MeHg in cockroaches. [ABSTRACT FROM AUTHOR]

Highlights • The histaminergic compounds injected in the cerebellum affect mice behavior in the open field. • Injections of chlorpheniramine into the cerebellar vermis increase locomotor and exploratory behaviors in mice. • Injections of VUF-8430 into the cerebellar vermis increase locomotor and exploratory behaviors in mice. Abstract The neural histaminergic system innervates the cerebellum, with a high density of fibers in the vermis and flocculus. The cerebellum participates in motor functions, but the role of the histaminergic system in this function is unclear. In the present study, we investigated the effects of intracerebellar histamine injections and H1, H2 and H3 receptor antagonist injections (chlorpheniramine, ranitidine, and thioperamide, respectively) and H4 receptor agonist (VUF-8430) on locomotor and exploratory behaviors in mice. The cerebellar vermis of male mice was implanted with guide cannula. After three days of recovery,the animals received microinjections of saline or histamine (experiment1), saline or chlorpheniramine (experiment 2), saline or ranitidine(experiment 3), saline or thioperamide (experiment 4), and saline or VUF-8430 (experiment 5) in different concentrations. Five minutes postinjection,the open field test was performed. The data were analyzed using one-way ANOVA and Duncan's post hoc test. The microinjections of histamine, ranitidine or thioperamide did not lead any behavioral effects at the used doses. In contrast, animals that received chlorpheniramine at the highest dose (0.16 nmol) and VUF-8430 at the highest dose (1.48 nmol)were more active in the open field apparatus, with an increase in the number of crossed quadrants, number of rearings and time spent in the central area of the arena, suggesting that chlorpheniramine and VUF-8430 modulates locomotor and exploratory behaviors in mice. [ABSTRACT FROM AUTHOR]

Synthetic organic insecticides, including pyrethroids, organophosphates, neonicotinoids and other types, have the potential to alter the ecosystems and many are harmful to humans. This study examines the developmental toxicity and neurotoxicity of three synthetic organic insecticides, including deltamethrin (DM), acephate (AP), and thiamethoxam (TM), using embryo-larval stages of zebrafish ( Danio rerio ). Results showed that DM exposure led to embryo development delay and a significant increase in embryo mortality at 24 and 48 h post-fertilization (hpf). DM and AP decreased embryo chorion surface tension at 24 hpf, along with the increase in hatching rate at 72 hpf. Moreover, DM caused ntl , shh, and krox20 misexpression in a dose-dependent manner with morphological deformities of shorter body length, smaller eyes, and larger head-body angles at 10 μg/L. TM did not show significant developmental toxicity. Furthermore, results of larval rest/wake assay indicated that DM (>0.1 μg/L) and AP (0.1 mg/L) increased activity behavior with different patterns. Interestingly, as an insect-specific pesticide, TM still could alter locomotor activity in zebrafish larvae at concentrations as low as 0.1 mg/L. Our results indicate that different types of synthetic organic insecticides could create different toxicity outcomes in zebrafish embryos and larvae. [ABSTRACT FROM AUTHOR]

Caffeine is an emerging contaminant in aquatic environments. The study utilized a validated method to investigate the presence and distribution of caffeine in the surface water of the Yellow and Bohai Seas, urban rivers, and the Yantai estuary area. The analytical method conforms to EPA guidelines and exhibits a limit of quantification that is 200 times lower than that of prior investigations. The study revealed that the highest concentration of 1436.4 ng/L was found in convergence of ocean currents in the Yellow and Bohai Seas. The presence of larger populations and the process of urban industrialization have been observed to result in elevated levels of caffeine in offshore regions, confirming that caffeine can serve as a potential indicator of anthropogenic contamination. Fish larvae exhibited hypoactivity in response to caffeine exposure at environmentally relevant concentrations. The study revealed that caffeine pollution can have adverse effects on marine and offshore ecosystems. This emphasizes the importance of decreasing neurotoxic pollution in the aquatic environment. [Display omitted] • A SPE-UPLC-APCI-MS method was developed in accordance with the guidelines of the EPA. • The levels of caffeine contamination in the Bohai and Yellow Seas were determined. • The maximum concentration of caffeine was found at the confluence of ocean currents. • Caffeine at environmental concentrations induces hypoactivity in zebrafish larvae. [ABSTRACT FROM AUTHOR]

Gamma-hydroxybutyric acid (GHB), both a metabolic precursor and product of gamma-aminobutyric acid (GABA), is a central nervous system depressant used for the treatment of narcolepsy-associated cataplexy and alcohol withdrawal. However, administration of GHB with alcohol (ethanol) is a major cause of hospitalizations related to GHB intoxication. In this study, we investigated locomotor behavior as well as metabolic and pharmacokinetic interactions following co-administration of GHB and ethanol in rats. The locomotor behavior of rats was evaluated following the intraperitoneal administration of GHB (sodium salt, 500 mg/kg) and/or ethanol (2 g/kg). Further, time-course urinary metabolic profiling of GHB and its biomarker metabolites glutamic acid, GABA, succinic acid, 2,4-dihydroxybutyric acid (OH-BA), 3,4-OH-BA, and glycolic acid as well as pharmacokinetic analysis were performed. GHB/ethanol co-administration significantly reduced locomotor activity, compared to the individual administration of GHB or ethanol. The urinary and plasma concentrations of GHB and other target compounds, except for 2,4-OH-BA, were significantly higher in the GHB/ethanol co-administration group than the group administered only GHB. The pharmacokinetic analysis results showed that the co-administration of GHB and ethanol significantly increased the half-life of GHB while the total clearance decreased. Moreover, a comparison of the metabolite-to-parent drug area under the curve ratios demonstrated that the metabolic pathways of GHB, such α- and β-oxidation, were inhibited by ethanol. Consequently, the co-administration of GHB and ethanol aggravated the metabolism and elimination of GHB and enhanced its sedative effect. These findings will contribute to clinical interpretation of GHB intoxication. [Display omitted] • GHB is a central nervous system depressant that is often misused with alcohol. • Ethanol significantly reduced GHB-induced locomotor activity. • Ethanol increased the half-life of GHB while the total clearance decreased. • Ethanol aggravated the metabolism of GHB and enhanced sedative effect. [ABSTRACT FROM AUTHOR]

Low-dose chronic lead (Pb) exposure interferes with the development of the nervous system, which may lead to learning disabilities, behavioral abnormalities, and mental retardation. Neurexins (Nrxns) are synaptic cell-adhesion molecules associated with neurological disorders. We hypothesized that Pb can affect the expression of nrxns during synapse formation and alter the phenotype behavior. Here, apoptosis, nrxns mRNA expression, and alterations of locomotion were examined after exposure to Pb in zebrafish embryos/larvae. To confirm the function of nrxn2a , rescue experiments were performed using β - nrxn2a mRNA microinjection. Pb exposure increased apoptosis and altered locomotor behavior in zebrafish larvae. Quantitative PCR showed that among several synaptic adhesion molecules, only nrxn2a were affected by Pb exposure. Moreover, exposure to Pb at 10 μmol/L upregulated mRNA expression of nrxn1a and nrxn3a at 24 h post fertilization (hpf) and downregulated expression at 48 hpf, whereas the expression remained unchanged at 72 hpf. Only the two isoforms of nrxn2a were downregulated by Pb at 10 μmol/L at all three time points. Rescue experiments showed that β-nrxn2a mRNA injection recovered the decreased locomotor activity and the increased apoptosis induced by Pb. In addition, overexpression of β - nrxn2a mRNA upregulated α - nrxn2a . These data indicated that Pb inhibited the expression of nrxn2a genes, which play a critical role in neural development, and further altered the behavior of zebrafish embryos/larvae. [ABSTRACT FROM AUTHOR]

Environmental exposure of fish to steroid hormones through wastewater and agricultural runoff may pose a health risk. Thus far, ecotoxicological studies have largely been focused on the disruption of the sex hormone system, but additional effects have been poorly investigated. Here we report on the effects of a series of different natural and synthetic steroid hormones on the locomotor behavior and the transcriptional levels of core clock genes in zebrafish eleuthero-embryos ( Danio rerio ). Of the 20 steroids analyzed, progestins and corticosteroids, including progesterone and cortisol, significantly decreased the locomotor activities of eleuthero-embryos at concentrations as low as 16 ng/L, while estrogens such as 17β-estradiol led to an increase. Consistently, progestins and corticosteroids displayed similar transcriptional effects on core clock genes, which were remarkably different from those of estrogens. Of these genes, per1a and nr1d2a displayed the most pronounced alterations. They were induced upon exposure to various progestins and corticosteroids and could be recovered using the progesterone receptor/glucocorticoid receptor antagonist mifepristone; this, however, was not the case for estrogens and the estrogen receptor antagonist 4-hydroxy-tamoxifen. Our results suggest that steroid hormones can modulate the circadian molecular network in zebrafish and provide novel insights into their mode of actions and potential environmental risks. [ABSTRACT FROM AUTHOR]

Larval zebrafish ( Danio rerio ) are a tool for assessing endocrine disruption during early development. Here, we investigated the extent to which a simple light/dark behavioral test at five days post fertilization could compliment current methods within the field. We exposed fertilized embryos to hormones (17β-estradiol, testosterone, dihydrotestosterone, 11-ketotestosterone, thyroxine, triiodothyronine, progesterone, and hydrocortisone) and other relevant compounds (17α ethinylestradiol, bisphenol A, bisphenol S, nonylphenol, flutamide, nilutamide, linuron, drospirenone, potassium perchlorate, mifepristone, and fadrozole) to screen for behavioral effects between 96 and 118 h post fertilization (hpf). With the exception of progesterone, all the hormones tested resulted in altered behaviors. However, some inconsistencies were observed regarding the age of the larvae at testing. For example, the xenoestrogens 17α- ethinylestradiol and nonylphenol had behavioral effects at 96 hpf, but not at 118 hpf. Furthermore, although thyroxine exposure had pronounced effects on behavior, the thyroid disruptor potassium perchlorate did not. Finally, we were unable to demonstrate a role of nuclear receptors following testosterone and 17α- ethinylestradiol exposure, as neither the androgen receptor antagonist flutamide nor the general estrogen receptor inhibitor fulvestrant (ICI) could rescue the observed behavioral effects, respectively. Similarly, molecular markers for androgen and estrogen disruption were upregulated at concentrations below which behavioral effects were observed. These results demonstrate hormones and endocrine disruptors can alter the behavior of larval zebrafish, but the mechanistic pathways remain unclear. [ABSTRACT FROM AUTHOR]

The dopamine transporter (DAT), which mediates the inactivation of released dopamine through its reuptake, is the primary molecular target for the actions of psychostimulants. An increasing number of studies support an essential role for phosphorylation of serines (Ser) in the distal amino (N) terminus of DAT in regulating its function. Still, the molecular details of the regulation of phosphorylation and its impact on function are not fully understood. To address this, we have developed and characterized two distinct phospho-antibodies that recognize human DAT when it is phosphorylated at Ser7 or Ser12. Our data show that treatment of cells with phorbol 12-myristate 13-acetate (PMA), amphetamine (AMPH) or okadaic acid (OA) leads to an increase in the phosphorylation of DAT at both residues and that these responses are dependent on the activity of protein kinase C. We also show that AMPH-induced and OA-induced phosphorylation of DAT are dependent on Ca 2+ /calmodulin-dependent protein kinase α. Our data further suggest that the lipid raft localization of DAT is necessary for efficient N-terminal phosphorylation and for the associated behavioral effects of AMPH, demonstrating the potential of these novel antibodies as powerful tools to study DAT regulation and function in vivo. [ABSTRACT FROM AUTHOR]

Zamzam water is well documented for plenty of medicinal value for curing illness. In the present study, the effects of perinatal consumption of Zamzam and normal drinking water by the pregnant mice on their offspring’s physical parameters, early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE) activity in the homogenize brain tissue and blood parameters were compared. To achieve that; Zamzam water was given to female Swiss-Webster strain mice as the only source of drinking fluid and the control animals were administered plain tap water. Treatment started from the first day of pregnancy and continued until the postnatal day fifteen of delivery. All offspring were subjected to various tests. The rate of body weight gain remained relatively unaffected until the second week of weaning period, however; in the last week the offspring exposed to Zamzam water gained significant body weight as compared to their control offspring. Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed pups remained unaffected as compared to the controls. The sensory motor reflexes in Zamzam exposed pups after birth and during the first two weeks of weaning period were significantly increased. Locomotor Activity Test performed in the male and female offspring after weaning period showed a significant decrease in the male and increase in the female on most of the elements of this test due to Zamzam exposure. AChE activity in the homogenized brain tissue and blood parameters were unaffected as compared to the controls, the present Zamzam effects in the offspring are possibly via in utero action and/or via mother’s milk. [ABSTRACT FROM AUTHOR]

[Display omitted] • TPhP triggered neurodevelopmental toxicity to zebrafish at different development stages. • TPhP further activated mitochondrial signaling pathways, resulting in visual impairment. • Retinoid acid (RA) signaling pathway may be novel target of TPhP exposure. • Apoptosis, oxidative stress and changes in related genes involved in TPhP neurotoxicity. • Abnormal behaviors contributed by co-regulation of visuomotor dysfunction and neuro-related genes. As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms. TPhP concentration gradient exposure reduced the survival rate, hatchability, heart rate, body length and eye distance of zebrafish embryos/larvae, and caused malformations of zebrafish larvae. TPhP also leads to abnormal locomotor behaviors, such as reduced swimming distance and swimming speed, and impaired panic avoidance reflex to high light stimulation. TPhP caused ROS accumulation in 96 hpf larvae and induced Nrf2-antioxidant response in zebrafish. In addition, TPhP further activated mitochondrial signaling pathways, which affected apoptosis in the zebrafish eye region, resulting in visual impairment. Neurodevelopmental (mbpa , syn2a , foxo3a and pax6a), Retinoid acid metabolism (cyp26a1 , raraa , rbp5 , rdh1 , crabp1a and rbp2a) and apoptosis-related genes (bcl2a , baxa and casp9) revealed the molecular mechanism of abnormal behavior and phenotypic symptoms, and also indicated that 96 hpf larvae are more sensitive than 7 dpf larvae. Thus, in the present study, we revealed the neurotoxic effects of TPhP at different early life stages in zebrafish, and zebrafish locomotor behavior impairments induced by TPhP exposure are attributed to co-regulation of visuomotor dysfunction and neuro-related genes. These results suggest that the safety of TPhP in organisms and even in humans needs to be further studied. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is an essential metal for organisms, but high levels can cause serious neurological damage. The aim of this study was to evaluate the effects of MnCl 2 exposure on cognition and exploratory behavior in adult and larval zebrafish and correlate these findings with brain accumulation of Mn, overall brain tyrosine hydroxylase (TH) levels, dopamine (DA) levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels and cell death markers in the nervous system. Adults exposed to MnCl 2 for 4 days (0.5, 1.0 and 1.5 mM) and larvae exposed for 5 days (0.1, 0.25 and 0.5 mM) displayed decreased exploratory behaviors, such as distance traveled and absolute body turn angle, in addition to reduced movement time and an increased number of immobile episodes in larvae. Adults exposed to MnCl 2 for 4 days showed impaired aversive long-term memory in the inhibitory avoidance task. The overall brain TH levels were elevated in adults and larvae evaluated at 5 and 7 days post-fertilization (dpf). Interestingly, the protein level of this enzyme was decreased in larval animals at 10 dpf. Furthermore, DOPAC levels were increased in adult animals exposed to MnCl 2 . Protein analysis showed increased apoptotic markers in both the larvae and adult nervous system. The results demonstrated that prolonged exposure to MnCl 2 leads to locomotor deficits that may be associated with damage caused by this metal in the CNS, particularly in the dopaminergic system. [ABSTRACT FROM AUTHOR]

The deep sea is the largest and at the same time least explored biome on Earth, but quantitative studies on the behavior of bathyal organisms are scarce because of the intrinsic difficulties related to in situ observations and maintaining animals in aquaria. In this study, we reported, for the first time, laboratory observations on locomotor rhythms and other behavioral observations (i.e. feeding, exploring and self-grooming) for the bathyal crab Geryon longipes . Crabs were collected on the middle-lower slope (720–1750 m) off the coast of Blanes (Spain). Inertial (18 h) water currents and monochromatic blue (i.e. 470 nm) light-darkness (24 h) cycles were simulated in two different experiments in flume tanks endowed with burrows. Both cycles were simulated in order to investigate activity rhythms regulation in Mediterranean deep-sea benthos. Crabs showed rhythmic locomotor activity synchronized to both water currents and light-darkness cycles. In general terms, feeding and exploring behaviors also followed the same pattern. Results presented here indicate the importance of local inertial (18 h) periodicity of water currents at the seabed as a temporal cue regulating the behavior of bathyal benthic fauna in all continental margin areas where the effects of tides is negligible. [ABSTRACT FROM AUTHOR]

Over-prescription and increased nonmedical use of oxycodone has become a major concern. Despite its increased use, preclinical data concerning oxycodone's effects are still limited, especially in rodent models. To address this, we examined oxycodone's effects on place preference, locomotor activation, corticosterone levels, and thermal analgesia across a range of doses (between 0.3 and 10 mg/kg) in gonadally intact, adult male and female C57BL/6J mice. Males and females showed oxycodone-induced conditioned place preference and did not show significant between-sex differences in their place preference behavior. During both CPP conditioning sessions and open field assay, locomotor activity was increased by 1, 3, and 10 mg/kg oxycodone in females and by 3 and 10 mg/kg oxycodone in males. Plasma corticosterone levels were higher in females (compared to males) at baseline as well as following acute oxycodone injection and open field testing. The time course of oxycodone-induced analgesia was similar in males and females, however the total antinociceptive effect (AUC 0 − 120 min ) was larger in males compared to females at the highest dose tested (10 mg/kg). Taken together, these data suggest that male and female mice are modestly different in their responses to oxycodone. [ABSTRACT FROM AUTHOR]

The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 μg L −1 or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 μg L −1 IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap) , Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development. [ABSTRACT FROM AUTHOR]

With the gradual ban on brominated flame retardants (FRs), the application of organophosphate flame retardants (OPFRs) has increased remarkably. Considering the structural similarity between OPFRs and organophosphate pesticides, hypotheses that OPFRs may interfere with neurodevelopment as organophosphate pesticides are reasonable. In this study, the neurotoxicity of three OPFRs, including tri-n-butyl phosphate (TNBP), tris (2-butoxyethyl) phosphate (TBOEP) and tris (2-chloroethyl) phosphate (TCEP), was evaluated in zebrafish larvae and then compared with the neurotoxicity of organophosphate pesticide chlorpyrifos (CPF). The results showed that similar to CPF, exposure to OPFRs for 5 days resulted in significant changes in locomotor behavior, either in free swimming or in photomotor response. However, given the transcriptional changes that occur in nervous system genes in response to OPFRs and CPF, as well as the altered enzyme activity of AChE and its mRNA level, the underlying mechanisms for neurotoxicity among these organophosphate chemicals might be varied. In summary, the results confirm the potential neurodevelopmental toxicity of OPFRs and underscore the importance of identifying the mechanistic targets of the OPFRs with specific moieties. Furthermore, as the neurobehavioral responses are well conserved among vertebrates and the exposure of children to OPFRs is significant, a thorough assessment of the risk of OPFRs exposure during early development should be highly emphasized in future studies. [ABSTRACT FROM AUTHOR]

The perfluorooctane sulfonate alternative, F–53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F–53B at four different concentrations (0, 0.15, 1.5, and 15 μg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F–53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53 , casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa , crybb , crygn , and mipa) and retinal development (pax6 , rx1 , gant1 , rho , opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F–53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis. [Display omitted] • F–53B induce small eye and histopathological abnormalities in larvae eye. • F–53B induce dose-dependent manner apoptosis in larvae eye. • mRNA levels involved in eye developmental were significantly changed. • F–53B induces locomotor behavior perturbed eye development disorders. [ABSTRACT FROM AUTHOR]

Movements and locomotor behaviour were studied in the most basal living frog family (Leiopelmatidae: Ascaphus + Leiopelmatidae), which includes two stream-dwelling species and several that have transitioned into terrestrial niches. These cryptic frogs remain immobile over 99.6% of the time above ground as they sit in wait of prey and only rarely use jumping to escape. Walking is their primary mode of locomotion. The two stream species, which are separated by deep time and extreme geographic distance, have nearly identical behavioural repertoires and locomotor performance, which included occasional jumping as a means to change foraging positions. The terrestrial species, one of which has become semi-arboreal, rarely jump in nature and rely on chemical and postural antipredator behaviours to avoid predation. If early frogs resembled leiopelmatids, they were not well versed in jumping. Locomotor behaviour and performance of leiopelmatid frogs do not support the hypothesis that frog jumping originally evolved primarily as a means to rapidly escape into water. Given the basal position of the leiopelmatids, the locomotor strategy of these cryptic, cold-adapted, belly-flopping anurans that usually walk may represent a successful initial step in the evolution of saltatorial locomotion in frogs. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies ( in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. [ABSTRACT FROM AUTHOR]

Zeolite imidazolate framework-8 (ZIF-8) is a nanomaterial of metal-organic frameworks (MOFs), which have various applications in drug delivery and water pollution remediation. However, little is known about its developmental neurotoxicity in aquatic organisms, especially on the low-level exposure. In the present study, we investigated the toxic effects of ZIF-8 NPs on the neuron development, behavioral traits, oxidative stress and gene expression in zebrafish embryos. Firstly, our results showed that ZIF-8 induced significantly embryonic malformations and abnormal development of nervous system in zebrafish embryos with a concentration-dependent manner. Meanwhile, the locomotor behavior was obviously inhibited while the anxiety behavior was greatly increased after ZIF-8 exposure. Secondly, the levels of ROS and antioxidant enzyme activities (CAT, SOD and MDA) together with AChE and ATPase were substantially increased in the ZIF-8 exposed groups. At the molecular level, ZIF-8 NPs could down-regulate the expression profiles of neural development-related genes (gap43, synapsin 2a and neurogenin 1) and PD-like related genes (dj-1, dynactin and parkin), but up-regulate the expression levels of neuro-inflammatory genes (nox-1, glip1a and glip1b) in larval zebrafish. In addition, we further explored the molecular mechanism of neurotoxicity induced by ZIF-8 with pharmacological experiments. The results showed that specific inhibition of ROS-mediated oxidative stress by the astaxanthin could reverse the expression patterns of ATPase, AChE and neurodevelopmental genes. Moreover, astaxanthin can partially rescue the ZIF-8-modulated locomotor behavior. Taken together, our results demonstrated that ZIF-8 had the potential to cause neurotoxicity in zebrafish embryos. These informations presented in this study will help to elucidate the molecular mechanisms of ZIF-8 nanoparticles exposure in zebrafish, which providing a scientific evaluation of its safety to aquatic ecosystems. [Display omitted] • ZIF-8 nanoparticles induced developmental neurotoxicity in zebrafish. • ZIF-8 NPs could increase the levels of oxidative stress and neuro-inflammatory genes. • ZIF-8 exposure could markedly decrease the locomotor behavior and increase the anxiety behavior. • Inhibition of ROS by astaxanthin can partially rescue the ZIF-8 induced neurobehavioral disorders. [ABSTRACT FROM AUTHOR]

To investigate the effect of voluntary physical activity (VPA) on inflammatory profile and the progression of experimental periodontal disease (PD) in mice. Male C57BL/6 mice were randomly distributed into Control; VPA; PD and PD/VPA groups. We registered VPA (total volume of revolutions) and average speed (revolutions/minute) in a free running wheel for 30 days. On the 15th day, animals from the PD and PD/VPA groups received ligatures on the upper second molars bilaterally. On the 30th day animals were euthanized, and PD progression was assessed by measuring alveolar bone loss (ABL - the linear distance between the cemento-enamel junction and the alveolar bone crest on the teeth buccal surface). Gene expression of RANKL (kappa nuclear factor B receptor) OPG (osteoprotegerin), IL-1β (interleukin 1 beta), IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) were evaluated by real-time PCR (quantitative Polymerase Chain Reaction - relative gene expression). The total volume of physical activity and the activity speed decreased along the seven days after ligature-placement (p < 0.05), returning to a similar pattern in relation to VPA group. Ligature placement produced significant bone resorption, and increased RANKL, IL-1β, IL-6 and TNF-α expression. VPA reduced ABL (p < 0,05) and the expression of TNF-α and IL-1β, whereas increased OPG expression. Animals induced to PD with access to the VPA wheel presented both lower gingival inflammation and less alveolar bone resorption in comparison to animals without access to the wheel. [ABSTRACT FROM AUTHOR]

Highlights: [•] A microswitch-based program was used to enhance adaptive behaviors in two girls with RS. [•] A new combination of microswitches promoting constructive engagement was assessed. [•] Object manipulation and ambulation responses improved during intervention phases. [•] The program had positive effects on mood and stereotyped behaviors in both participants. [•] The assistive technology system was suitable and affordable for girls with Rett syndrome. [Copyright &y& Elsevier]

Abstract: Dogs exhibit biorhythms like diurnal sleep/wake and rest/activity behavior patterns with circadian rhythmicity and, similar to other mammalian species, show age-dependent changes in activity rhythms. This study sought to further characterize night/day locomotor activity patterns in adult dogs of various ages, and to examine the effect of feeding frequency (once vs. twice). Three groups (early adults [EA], 1.5-4.5 years; late adults [LA], 7-9 years; senior, 11-14 years) of beagles (N = 48) wore the Actiwatch activity monitoring system for 3 days while housed indoors with 12-hour light/dark schedule. Activity recording devices were used to collect actigraphy data when dogs were on a once- or twice-daily feeding regimen. All dogs demonstrated a circadian activity pattern with high levels of daytime activity and low levels of nighttime activity. The main effect of age differed for both daytime (P < 0.0001) and nighttime (P = 0.002) activity counts. Daytime activity in senior dogs was 17% and 42% lower compared with LA and EA dogs, respectively. With nighttime activity, both LA and seniors had significantly lower counts compared with the EA. Compared to once-daily feeding, twice-daily feeding significantly increased night activity, night/day activity ratio, and activity counts 60 minutes before the light phase across all 3 age-groups. This study provides a comprehensive characterization of age-related changes in locomotor behavior patterns in dogs and uniquely demonstrates that frequency of feeding can influence nighttime activity levels, which is partially associated with level of prelight onset of activity. [Copyright &y& Elsevier]

Abstract: We present a software (ETHOWATCHER®) developed to support ethography, object tracking and extraction of kinematic variables from digital video files of laboratory animals. The tracking module allows controlled segmentation of the target from the background, extracting image attributes used to calculate the distance traveled, orientation, length, area and a path graph of the experimental animal. The ethography module allows recording of catalog-based behaviors from environment or from video files continuously or frame-by-frame. The output reports duration, frequency and latency of each behavior and the sequence of events in a time-segmented format, set by the user. Validation tests were conducted on kinematic measurements and on the detection of known behavioral effects of drugs. This software is freely available at www.ethowatcher.ufsc.br. [Copyright &y& Elsevier]

Abstract: We describe a low-cost system for monitoring the behavioral activity of the fruit fly, Drosophila melanogaster. The system is readily adaptable to one or more cameras for simultaneous recordings of behavior from different angles and can be used for monitoring multiple individuals in a population at the same time. Signal processing allows discriminating between active and inactive periods during locomotion or flying, and quantification of subtler movements related to changes in position of the wings or legs. The recordings can be taken continuously over long periods of time and can thus provide information about the dynamics of a population. The system was used to monitor responses to caffeine, changes in temperature and g-force, and activity in a variable size population. [Copyright &y& Elsevier]

Abstract: Use of drugs of abuse in combination is common among recreational users and addicts. The combination of a psychomotor stimulant with an opiate, known as a ‘speedball,’ reportedly produces greater effects than either drug alone and has been responsible for numerous deaths. Historically, the most popular speedball combination is that of cocaine and heroin. However, with the growing popularity of methamphetamine in recent years, there has been increased use of this drug in combination with other drugs of abuse, including opiates. Despite this, relatively little research has examined interactions between methamphetamine and opiates. In the current research, behavioral interactions between methamphetamine and the prototypical opiate, morphine, were examined across a variety of dose combinations in Sprague–Dawley rats. The combination of methamphetamine and morphine produced stimulation of behavior that was dramatically higher than either drug alone; however, the magnitude of the interaction was dependent on the dose of the drugs and the specific behaviors examined. The results demonstrate complex behavioral interactions between these drugs, but are consistent with the idea that this combination is used because it produces a greater effect than either drug alone. [Copyright &y& Elsevier]

Abstract: The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual behavior. [Copyright &y& Elsevier]

Abstract: Botulinum toxin is an agent that is typically encountered in two settings: as an agent that can cause disease (e.g. botulism), and as an agent that can be used to treat disease (i.e., a variety of neurologic disorders). In both cases it would be advantageous to develop a sound understanding of the mechanisms by which antibodies neutralize the toxin. In the present study, recombinant antigens were used to generate antibodies against the carboxyterminal half of the toxin heavy chain (HC50), the entire toxin light chain (LC), and the HA17, HA35 and HA70 components of the progenitor toxin complex. These antibodies were then evaluated for their respective abilities to alter botulinum toxin-induced changes in locomotor behavior in mice. The botulinum toxin type A complex was shown to produce dose-dependent depression of locomotor behavior within the dose range of 0.3–0.7 mouse LD50 units. At a dose of 0.5 LD50, the toxin typically reduced running behavior by 90% or more, and full recovery was not observed for approximately 4 weeks. Mice that were actively or passively vaccinated against the HC50 polypeptide were resistant to toxin action, presumably because the antibodies occluded the toxin binding domain. Interestingly, mice that were actively or passively vaccinated against LC were also resistant to toxin action. This effect may have been due to steric hindrance of the binding process. There was no scenario in which anti-HA antibodies altered the effects of toxin on locomotor behavior. This absence of effect was likely due to the fact that HAs and neurotoxin in the progenitor toxin complex spontaneously dissociate in physiologic media. [Copyright &y& Elsevier]

Abstract: This paper is the 32nd consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2009 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular–biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section ), and the roles of these opioid peptides and receptors in pain and analgesia (Section ); stress and social status (Section ); tolerance and dependence (Section ); learning and memory (Section ); eating and drinking (Section ); alcohol and drugs of abuse (Section ); sexual activity and hormones, pregnancy, development and endocrinology (Section ); mental illness and mood (Section ); seizures and neurologic disorders (Section ); electrical-related activity and neurophysiology (Section ); general activity and locomotion (Section ); gastrointestinal, renal and hepatic functions (Section ); cardiovascular responses (Section ); respiration and thermoregulation (Section ); and immunological responses (Section ). [ABSTRACT FROM AUTHOR]

Abstract: Burrows are used by many mammals to escape predation, cache food and for parturition. Although the construction of burrows has been studied in some taxa, the locomotion while inside of them has received scant attention. In this study we collected simultaneous video and force data to characterize gaits, kinematics, peak ground reaction forces (GRFs) and external mechanical energy profiles in the domestic ferret, an animal that displays the typical morphology and behaviors associated with subterranean adaptations in mustelines. We compared kinematics and kinetics between locomotion in two experimental conditions: subterranean, simulated by a Plexiglass tunnel designed such that the ferrets’ peak back height was reduced by 40% and hip height by 25%, and epigean, or unconstrained overground. Despite the large change in posture, a striking number of gait and force variables were not statistically different between experimental conditions. In both subterranean and epigean conditions, the ferrets in our study traveled at similar average velocities (∼0.8ms−1), preferred to use a lateral-sequence diagonal-couplet gait, and were more likely to demonstrate the in-phase fluctuations of external mechanical energy indicative of running mechanics (68% of all trials). The ferrets conformed to gait and mechanical patterns seen in a variety of other small (<1kg) mammals rather than being unique, despite the divergent morphology of mustelines. Our results demonstrated biodynamically similar locomotion in both epigean and subterranean conditions and support the hypothesis that ferrets possess adaptations for tunnel locomotion. [Copyright &y& Elsevier]

Abstract: This paper provides an overview of studies using programs with treadmills or walkers with microswitches and contingent stimulation to foster locomotor behavior of children with developmental disabilities. Twenty-six studies were identified in the period 2000–2008 (i.e., the period in which research in this area has actually taken shape). Twenty-one of the studies involved the use of treadmills (i.e., 13 were aimed at children with cerebral palsy, 6 at children with Down syndrome, and 2 at children with Rett syndome or cerebellar ataxia). The remaining five studies concerned the use of walkers with microswitches and contingent stimulation with children with multiple disabilities. The outcomes of the studies tended to be positive but occasional failures also occurred. The outcomes were analyzed considering the characteristics of the approaches employed, the implications of the approaches for the participants’ overall functioning situation (development), as well as methodological and practical aspects related to those approaches. Issues for future research were also examined. [Copyright &y& Elsevier]

Antineoplastics treat cancers and enter aquatic ecosystems through wastewater and hospital effluent. Risks associated with antineoplastics are not well characterized in aquatic organisms. We conducted zebrafish embryo/larvae toxicity assays to evaluate responses to cyclophosphamide (0.01–50 µM). Zebrafish survival was affected by 5 µM cyclophosphamide and deformities were noted at > 1 µM. Oxidative respiration remained unchanged in embryos with exposure up to 200 µM. Reactive oxygen species were not increased by 50 µM cyclophosphamide exposure. More than 15 oxidative stress and immune-related transcripts were measured. Superoxide dismutase 2 and heat shock protein 70 and 90a were induced in larvae by cyclophosphamide. Immune-related transcripts were assessed due to immunosuppressive properties of cyclophosphamide, and mmp9 and myd88 levels were altered in expression. Hyperactivity of larvae was noted following 5 µM cyclophosphamide exposure. There was no change in anxiety-related endpoints (light-dark preference). Risks for larval fish exposed to cyclophosphamide in the environment may be low. [Display omitted] • Cyclophosphamide is an antineoplastic pharmaceutical detected in aquatic environments. • Cyclophosphamide did not affect mitochondrial respiration up to 50 µM. • Expression levels of ache, hsp70, hsp90a, and sod2 were altered with exposure to cyclophosphamide. • Cyclophosphamide induced hyperactivity at 5 µM but did not affect anxiety-like behaviors. • Cyclophosphamide did not impact sub-lethal endpoints investigated at environmental levels. [ABSTRACT FROM AUTHOR]

Abstract: Neuropeptide Y (NPY) is involved in the regulation of emotional behavior, and there is indirect evidence for a role of NPY in the cerebral responses to peripheral immune challenge. Since the NPY receptors involved in these reactions are not known, we investigated the effect of Escherichia coli lipopolysaccharide (LPS) on emotional, locomotor and social behavior, body temperature and circulating corticosterone in female Y2 (Y2−/−) and Y4 (Y4−/−) receptor knockout mice. LPS (0.1mg/kg injected IP 2.5h before testing) increased rectal temperature in control and Y4−/− mice to a larger degree than in Y2−/− animals. Both Y2−/− and Y4−/− mice exhibited reduced anxiety-related and depression-like behavior in the open field, elevated plus-maze and tail suspension test, respectively. While depression-like behavior was not changed by LPS, anxiety-related behavior was enhanced by LPS in Y2−/−, but not control and Y4−/− animals. Y2−/− mice were also particularly susceptible to the effect of LPS to attenuate locomotor behavior and social interaction with another mouse. The corticosterone response to LPS was blunted in Y2−/− mice which presented elevated levels of circulating corticosterone following vehicle treatment. These data show that Y2−/− mice are particularly sensitive to the effects of LPS-evoked immune stress to attenuate locomotion and social interaction and to increase anxiety-like behavior, while the LPS-induced rise of temperature and circulating corticosterone is suppressed by Y2 receptor knockout. Our observations attest to an important role of endogenous NPY acting via Y2 receptors in the cerebral response to peripheral immune challenge. [Copyright &y& Elsevier]

Abstract: The present study evaluated the effects of intracranial administration of amphetamine (AMPH) on paced mating behavior and open field activity in sexually receptive female rats. In Experiment 1, AMPH (0.5 µl of 10 µg/µl) or vehicle was infused bilaterally into the medial preoptic area (mPOA). In Experiments 2 and 3, AMPH (0.5 µl of 40 µg/µl) or vehicle was infused bilaterally into the shell region of the nucleus accumbens (NAc) or core region of the NAc, respectively. In Experiment 1, infusions of AMPH into the mPOA increased the latency to return to the male following sexual stimulation without affecting locomotor activity in the open field test. However, when AMPH was infused 3.0 mm dorsal to the mPOA, no effects were observed. In Experiments 2 and 3, infusions of AMPH into the NAc shell or core significantly increased locomotor activity during the open field test but failed to affect most measures of paced mating behavior. Together these results suggest that amphetamine-stimulate dopamine release in the mPOA but not in the NAc alters paced mating behavior, confirming previous conclusions that the mPOA plays a critical role in female sexual behavior, whereas the NAc plays a relatively limited role. [Copyright &y& Elsevier]