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Earth's rotation shapes a 24‐h cycle, governing circadian rhythms in organisms. In mammals, the core clock genes, CLOCK and BMAL1, are regulated by PERIODs (PERs) and CRYPTOCHROMEs (CRYs), but their roles remain unclear in the diamondback moth, Plutella xylostella. To explore this, we studied P. xylostella, which possesses a simplified circadian system compared to mammals. In P. xylostella, we observed rhythmic expressions of the Pxper and Pxcry2 genes in their heads, with differing phases. In vitro experiments revealed that PxCRY2 repressed monarch butterfly CLK:BMAL1 transcriptional activation, while PxPER and other CRY‐like proteins did not. However, PxPER showed an inhibitory effect on PxCLK/PxCYCLE. Using CRISPR/Cas9, we individually and in combination knocked out Pxper and Pxcry2, then conducted gene function studies and circadian transcriptome sequencing. Loss of either Pxper or Pxcry2 eliminated the activity peak after lights‐off in light–dark cycles, and Pxcry2 loss reduced overall activity. Pxcry2 was crucial for maintaining endogenous rhythms in constant darkness. Under light–dark conditions, 1 098 genes exhibited rhythmic expression in wild‐type P. xylostella heads, with 749 relying on Pxper and Pxcry2 for their rhythms. Most core clock genes lost their rhythmicity in Pxper and Pxcry2 mutants, while Pxcry2 sustained rhythmic expression, albeit with reduced amplitude and altered phase. Additionally, rhythmic genes were linked to biological processes like the spliceosome and Toll signaling pathway, with these rhythms depending on Pxper or Pxcry2 function. In summary, our study unveils differences in circadian rhythm regulation by Pxper and Pxcry2 in P. xylostella. This provides a valuable model for understanding circadian clock regulation in nocturnal animals. [ABSTRACT FROM AUTHOR]

Objectives: Many early fossil hominins are associated with savanna‐mosaic paleohabitats, and high sexual dimorphism that may reflect differences in positional behavior between sexes. However, reconstructions of hominin behavior and the selective pressures they faced in an open habitat are limited by a lack of studies of extant apes living in contemporary, analogous habitats. Here, we describe adult chimpanzee positional behavior in the savanna‐mosaic habitat of the Issa Valley, Tanzania, to test whether Issa chimpanzees show larger sex‐differences in positional behavior than their forest‐dwelling counterparts. Materials and Methods: We quantified and compared adult locomotor and postural behavior across sexes (6 females, 7 males) in the riparian forest (closed) and miombo woodland (open) vegetation types at Issa Valley (13,743 focal observations). We then compared our results to published data of chimpanzee communities living in more forested habitats. Results: Issa females and males both spent less time arboreally in open vegetation and showed similar locomotor and postural behavior on the same substrates, notably using a high level of suspensory locomotion when arboreal. Females were, however, more arboreal than males during locomotor behavior, as well as compared with females from other communities. Issa males behaved similarly to males from other communities. Conclusion: Results suggest that open habitats do not elicit less arboreal behaviors in either sex, and may even select for suspensory locomotion to effectively navigate an open canopy. An open habitat may, however, increase sex differences in positional behavior by driving female arboreality. We suggest this is because of higher energetic demands and predator pressures associated with open vegetation, which are likely exaggerated for reproducing females. These results have implications for the interpretation of how sexual dimorphism may influence reconstructions of hominin positional behavior. [ABSTRACT FROM AUTHOR]

This study investigated the effects of environmental changes on zebrafish larval behavior, using single-factor and orthogonal experiments to assess locomotion during temperature and pH changes. In single-factor experiments, zebrafish larvae were exposed to variations in temperature (22 to 30 °C) and pH levels (6.0, 7.0, 9.0). The simultaneous temperature and pH changes were investigated by orthogonal tests. In both experiments, each zebrafish larva was recorded in three 5 min videos at different stages (before exposure, during short-term exposure (10 min), and after long-term exposure (60 min)). You Look Only Once (YOLOv5) and Deep Simple Online Real Time Tracking (DeepSORT) models were adopted to develop a zebrafish larva tracking system, and YOLOv5 was improved in two aspects of anchor clustering and network structure. The tracking accuracy of the tracking system for small targets effectively improved, reaching more than 98% MOTA (Multiple Object Tracking Accuracy). Principal Component Analysis (PCA) was employed to extract three behavioral features from 13 motion parameters, namely motion activity, edge behavior, and motion direction preference. Our findings reveal that lower temperatures and acidic conditions both led to a decrease in motion behavioral activity, and the former also increased edge behavior. Conversely, elevated temperatures and alkaline conditions had a muted impact on these behaviors. Interestingly, concurrent changes in temperature and pH significantly altered directional preference. Additionally, we observed that lower temperatures elicited distinct temporal behavioral patterns at a constant pH level. In summary, we recommend the precise control and explicit reporting of ambient temperature and pH in both breeding devices and experimental wells to minimize the environmental impact on zebrafish behavior and enhance experiment repeatability and reliability. [ABSTRACT FROM AUTHOR]

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Simple Summary: Over the years, research from other areas has suggested that tadpole shrimps could be a useful model to detect and evaluate the effects of aquatic contamination and environmental health. Its size, active swimming, short generation time, and easy lab maintenance make it an attractive alternative to the use of higher sentient animals. This investigation has thus aimed at evaluating the sensitivity of Triops longicaudatus to potassium dichromate, a common contaminant in aquatic systems, also used as reference compound in ecotoxicology. Lethal and sublethal exposure assays were carried out and biochemical to apical endpoints with an impact at the population level were measured. We found negative impacts in the growth rate, delayed reproductive maturity, and alteration in the locomotor behavior upon exposure to potassium dichromate. The sensitivity of the species was higher than that of various freshwater animals commonly used in toxicity testing. Behavior appeared as the most sensitive response to chromium exposure, discriminating well the test concentrations from the control group and from each other. The tadpole shrimp Triops longicaudatus is a freshwater crustacean with fast embryonic and larval development, short life cycle, and high fecundity. They are very active swimmers of a reasonable size, easy to spot and record. Such characteristics make it a promising candidate as an experimental model in ecotoxicology to evaluate the effects of aquatic pollutants, particularly using its locomotor behavior as an endpoint. To evaluate the sensitivity of T. longicaudatus and develop endpoints of interest, we conducted exposure experiments with lethal and sub-lethal concentrations of potassium dichromate, a compound known for its ecotoxicological importance and as a hexavalent chromium source. The endpoints evaluated were mortality, growth, sexual maturation, reproductive output, cholinesterase activity and locomotor/swimming behavior. The 96 h median lethal concentration was found to be 65 µg/L. Furthermore, exposure to potassium dichromate at higher concentrations had a significant negative impact on the growth rate of T. longicaudatus in terms of both body mass and length. The time for maturation was also delayed at higher concentrations. In addition, locomotor behavior allowed for the discrimination of all tested chromium concentrations and the control group and from each other, proving to be the most sensitive endpoint. Overall, the data support the potential of T. longicaudatus as a model for ecotoxicity testing, using apical endpoints with impact at the population level; in particular, results suggest that behavior assessments in this species might be useful for detecting hazardous compounds in environmental monitoring of freshwater ecosystems. [ABSTRACT FROM AUTHOR]

Global warming has heightened the severity and frequency of extreme high-temperature events, presenting challenges to fish survival and negatively affecting the production of fishery. Gymnocypris eckloni, native to the Tibetan Plateau, is widely cultured in southwest China. Its sensitivity to heat makes it a suitable model for studying the impact of high temperatures on fish. The heart is a vital organ for survival, while is relatively understudied concerning the impact of high temperatures on fish hearts. In this study, G. eckloni was subjected to a seven-day exposure to 27 °C followed by a transfer to 18 °C for a seven-day recovery period. Behavioral tests revealed a significant increase in locomotor speed, distance, and respiratory rate of G. eckloni at 27 °C. Serum indices exhibited significantly elevated stress indicators (cortisol) and kinases associated with heart damage (lactate dehydrogenase, lactate dehydrogenase isoenzyme 1, creatine kinase, creatine kinase isoenzyme, and aspartate transaminase) at 27 °C, and histological analyses have confirmed the occurrence of heart damage subjected to high temperatures. After 7 days of recovery, most of these indicators showed a significant decrease compared to the heat stress group, with no significant differences observed compared to the control group. Transcriptomic analyses have revealed the widespread involvement of ferroptosis, P53 signaling pathway, oxidative phosphorylation, myocardial contraction, and DNA repair pathway in the response of G. eckloni to high temperatures. Our study offers a systematic exploration of the effects of heat stress on G. eckloni, providing valuable insights for the cultivation of high-altitude fish.

Depressive disorders are among the most important psychiatric problems. In everyday clinical practice, their symptoms and, respectively, their response to pharmacological treatment are both evaluated and measured subjectively. In the present paper, we apply a new approach for objective monitoring of the pharmacological-treatment response in patients with recurrent depressions. The applied method is user-friendly, easy-to-perform, and not time-consuming (1 test = 1 min), thus allowing repeatable examinations of many patients. The results show that the pre-treatment examination could discriminate between patients and healthy controls by revealing objectively measurable psychomotor retardation (in terms of locomotor hypo-activity and brady-reactivity) in the depressive group. After effective psychopharmacological treatment in a psychiatric clinic, the revealed psychomotor retardation is significantly improved (although not fully normalized) during the post-treatment examination at the time of discharge. The conclusion is that the new approach is reliable and sensitive enough to serve as a surrogate pharmacodynamic biomarker in patients with recurrent depressions. [ABSTRACT FROM AUTHOR]

This study investigated the effects of environmental changes on zebrafish larval behavior, using single-factor and orthogonal experiments to assess locomotion during temperature and pH changes. In single-factor experiments, zebrafish larvae were exposed to variations in temperature (22 to 30 °C) and pH levels (6.0, 7.0, 9.0). The simultaneous temperature and pH changes were investigated by orthogonal tests. In both experiments, each zebrafish larva was recorded in three 5 min videos at different stages (before exposure, during short-term exposure (10 min), and after long-term exposure (60 min)). You Look Only Once (YOLOv5) and Deep Simple Online Real Time Tracking (DeepSORT) models were adopted to develop a zebrafish larva tracking system, and YOLOv5 was improved in two aspects of anchor clustering and network structure. The tracking accuracy of the tracking system for small targets effectively improved, reaching more than 98% MOTA (Multiple Object Tracking Accuracy). Principal Component Analysis (PCA) was employed to extract three behavioral features from 13 motion parameters, namely motion activity, edge behavior, and motion direction preference. Our findings reveal that lower temperatures and acidic conditions both led to a decrease in motion behavioral activity, and the former also increased edge behavior. Conversely, elevated temperatures and alkaline conditions had a muted impact on these behaviors. Interestingly, concurrent changes in temperature and pH significantly altered directional preference. Additionally, we observed that lower temperatures elicited distinct temporal behavioral patterns at a constant pH level. In summary, we recommend the precise control and explicit reporting of ambient temperature and pH in both breeding devices and experimental wells to minimize the environmental impact on zebrafish behavior and enhance experiment repeatability and reliability.

The precise control of motor movements is of fundamental importance to all behaviors in the animal kingdom. Efficient motor behavior depends on dedicated neuronal circuits - such as those in the cerebellum - that are controlled by extensive genetic programs. Autosomal recessive cerebellar ataxias (ARCAs) provide a valuable entry point into how interactions between genetic programs maintain cerebellar motor circuits. We previously identified a striking enrichment of DNA repair genes in ARCAs. How dysfunction of ARCA-associated DNA repair genes leads to preferential cerebellar dysfunction and impaired motor function is however unknown. The expression of ARCA DNA repair genes is not specific to the cerebellum. Only a limited number of animal models for DNA repair ARCAs exist, and, even for these, the interconnection between DNA repair defects, cerebellar circuit dysfunction, and motor behavior is barely established. We used Drosophila melanogaster to characterize the function of ARCA-associated DNA repair genes in the mushroom body (MB), a structure in the Drosophila central brain that shares structural features with the cerebellum. Here, we demonstrate that the MB is required for efficient startle-induced and spontaneous motor behaviors. Inhibition of synaptic transmission and loss-of-function of ARCA-associated DNA repair genes in the MB affected motor behavior in several assays. These motor deficits correlated with increased levels of MB DNA damage, MB Kenyon cell apoptosis and/or alterations in MB morphology. We further show that expression of genes involved in glutamate signaling pathways are highly, specifically, and persistently elevated in the postnatal human cerebellum. Manipulation of glutamate signaling in the MB induced motor defects, Kenyon cell DNA damage and apoptosis. Importantly, pharmacological reduction of glutamate signaling in the ARCA DNA repair models rescued the identified motor deficits, suggesting a role for aberrant glutamate signaling in ARCA-DNA repair disorders. In conclusion, our data highlight the importance of ARCA-associated DNA repair genes and glutamate signaling pathways to the cerebellum, the Drosophila MB and motor behavior. We propose that glutamate signaling may confer preferential cerebellar vulnerability in ARCA-associated DNA repair disorders. Targeting glutamate signaling could provide an exciting therapeutic entry point in this large group of so far untreatable disorders. [ABSTRACT FROM AUTHOR]

The precise control of motor movements is of fundamental importance to all behaviors in the animal kingdom. Efficient motor behavior depends on dedicated neuronal circuits – such as those in the cerebellum – that are controlled by extensive genetic programs. Autosomal recessive cerebellar ataxias (ARCAs) provide a valuable entry point into how interactions between genetic programs maintain cerebellar motor circuits. We previously identified a striking enrichment of DNA repair genes in ARCAs. How dysfunction of ARCA-associated DNA repair genes leads to preferential cerebellar dysfunction and impaired motor function is however unknown. The expression of ARCA DNA repair genes is not specific to the cerebellum. Only a limited number of animal models for DNA repair ARCAs exist, and, even for these, the interconnection between DNA repair defects, cerebellar circuit dysfunction, and motor behavior is barely established. We used Drosophila melanogaster to characterize the function of ARCA-associated DNA repair genes in the mushroom body (MB), a structure in the Drosophila central brain that shares structural features with the cerebellum. Here, we demonstrate that the MB is required for efficient startle-induced and spontaneous motor behaviors. Inhibition of synaptic transmission and loss-of-function of ARCA-associated DNA repair genes in the MB affected motor behavior in several assays. These motor deficits correlated with increased levels of MB DNA damage, MB Kenyon cell apoptosis and/or alterations in MB morphology. We further show that expression of genes involved in glutamate signaling pathways are highly, specifically, and persistently elevated in the postnatal human cerebellum. Manipulation of glutamate signaling in the MB induced motor defects, Kenyon cell DNA damage and apoptosis. Importantly, pharmacological reduction of glutamate signaling in the ARCA DNA repair models rescued the identified motor deficits, suggesting a role for aberrant glutamate signaling in ARCA-DNA repair disorders. In conclusion, our data highlight the importance of ARCA-associated DNA repair genes and glutamate signaling pathways to the cerebellum, the Drosophila MB and motor behavior. We propose that glutamate signaling may confer preferential cerebellar vulnerability in ARCA-associated DNA repair disorders. Targeting glutamate signaling could provide an exciting therapeutic entry point in this large group of so far untreatable disorders.

Introduction: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology. Methods: The GABAB receptor agonist R-Baclofen and the selective agonist for the 5HT7 serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD. To evaluate the efficacy of these compounds in more details, we treated BTBR TC Itpr3tf/J and B6.129P2-Fmr1tm1Cgr/J mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests. Results: BTBR mice showed motor deficits, elevated anxiety, and highly repetitive behavior of self-grooming. Fmr1-KO mice exhibited decreased anxiety and hyperactivity. Additionally, Fmr1-KO mice's ultrasonic vocalizations were impaired suggesting a reduced social interest and communication of this strain. Acute LP-211 administration did not affect the behavioral abnormalities observed in BTBR mice but improved repetitive behavior in Fmr1-KO mice and showed a trend to change anxiety of this strain. Acute R-Baclofen treatment improved repetitive behavior only in Fmr1-KO mice. Conclusion: Our results add value to the current available data on these mouse models and the respective compounds. Yet, additional studies are needed to further test R-Baclofen and LP-211 as potential treatments for ASD therapy. [ABSTRACT FROM AUTHOR]

Milk oligosaccharides are a complex class of carbohydrates that act as bioactive factors in numerous defensive and physiological functions, including brain development. Early nutrition can modulate nervous system development and can lead to epigenetic imprinting. We attempted to increase the sialylated oligosaccharide content of zebrafish yolk reserves, with the aim of evaluating any short-term effects of the treatment on mortality, locomotor behavior, and gene expression. Wild-type embryos were microinjected with saline solution or solutions containing sialylated milk oligosaccharides extracted from human and bovine milk. The results suggest that burst activity and larval survival rates were unaffected by the treatments. Locomotion parameters were found to be similar during the light phase between control and treated larvae; in the dark, however, milk oligosaccharide-treated larvae showed increased test plate exploration. Thigmotaxis results did not reveal significant differences in either the light or the dark conditions. The RNA-seq analysis indicated that both treatments exert an antioxidant effect in developing fish. Moreover, sialylated human milk oligosaccharides seemed to increase the expression of genes related to cell cycle control and chromosomal replication, while bovine-derived oligosaccharides caused an increase in the expression of genes involved in synaptogenesis and neuronal signaling. These data shed some light on this poorly explored research field, showing that both human and bovine oligosaccharides support brain proliferation and maturation. [ABSTRACT FROM AUTHOR]

Fluoride is one of the major toxicants in the environment and is often found in drinking water at higher concentrations. Living organisms including humans exposed to high fluoride levels are found to develop mild-to-severe detrimental pathological conditions called fluorosis. Fluoride can cross the hematoencephalic barrier and settle in various brain regions. This accumulation affects the structure and function of both the central and peripheral nervous systems. The neural ultrastructure damages are reflected in metabolic and cognitive activities. Hindrances in synaptic plasticity and signal transmission, early neuronal apoptosis, functional alterations of the intercellular signaling pathway components, improper protein synthesis, dyshomeostasis of the transcriptional and neurotrophic factors, oxidative stress, and inflammatory responses are accounted for the fluoride neurotoxicity. Fluoride causes a decline in brain functions that directly influence the overall quality of life in both humans and animals. Animal studies are widely used to explore the etiology of fluoride-induced neurotoxicity. A good number of these studies support a positive correlation between fluoride intake and toxicity phenotypes closely associated with neurotoxicity. However, the experimental dosages highly surpass the normal environmental concentrations and are difficult to compare with human exposures. The treatment procedures are highly dependent on the dosage, duration of exposure, sex, and age of specimens among other factors which make it difficult to arrive at general conclusions. Our review aims to explore fluoride-induced neuronal damage along with associated histopathological, behavioral, and cognitive effects in experimental models. Furthermore, the correlation of various molecular mechanisms upon fluoride intoxication and associated neurobehavioral deficits has been discussed. Since there is no well-established mechanism to prevent fluorosis, phytochemical-based alleviation of its characteristic indications has been proposed as a possible remedial measure. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is one of the most widely produced chemicals in the world used in the production of epoxy resins and polycarbonate plastics. BPA is easily migrated from the outer packaging to the contents. Due to the lipophilic property, BPA is easily accumulated in organisms. Perinatal low-dose BPA exposure alters brain neural development in later generations. In this study, after BPA treatment, the spontaneous movement of zebrafish larvae from the cleavage period to the segmentation period (1–24 hpf) was significantly decreased, with speed decreasing by 18.97% and distance decreasing between 18.4 and 29.7% compared to controls. Transcriptomics analysis showed that 131 genes were significantly differentially expressed in the exposed group during the 1–24 hpf period, among which 39 genes were significantly upregulated and 92 genes were significantly downregulated. The GO enrichment analysis, gene function analysis and real-time quantitative PCR of differentially expressed genes showed that the mRNA level of guanine deaminase (cypin) decreased significantly in the 1–24 hpf period. Moreover, during the 1–24 hpf period, BPA exposure reduced guanine deaminase activity. Therefore, we confirmed that cypin is a key sensitive gene for BPA during this period. Finally, the cypin mRNA microinjection verified that the cypin level of zebrafish larvae was restored, leading to the restoration of the locomotor activity. Taken together, the current results show that the sensitive period of BPA to zebrafish embryos is from the cleavage period to the segmentation period (1–24 hpf), and cypin is a potential target for BPA-induced neurodevelopmental toxicity. This study provides a potential sensitive period and a potential target for the deep understanding of neurodevelopmental toxicity mechanisms caused by BPA. [ABSTRACT FROM AUTHOR]

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]

The tadpole shrimp Triops longicaudatus is a freshwater crustacean with fast embryonic and larval development, short life cycle, and high fecundity. They are very active swimmers of a reasonable size, easy to spot and record. Such characteristics make it a promising candidate as an experimental model in ecotoxicology to evaluate the effects of aquatic pollutants, particularly using its locomotor behavior as an endpoint. To evaluate the sensitivity of T. longicaudatus and develop endpoints of interest, we conducted exposure experiments with lethal and sub-lethal concentrations of potassium dichromate, a compound known for its ecotoxicological importance and as a hexavalent chromium source. The endpoints evaluated were mortality, growth, sexual maturation, reproductive output, cholinesterase activity and locomotor/swimming behavior. The 96 h median lethal concentration was found to be 65 µg/L. Furthermore, exposure to potassium dichromate at higher concentrations had a significant negative impact on the growth rate of T. longicaudatus in terms of both body mass and length. The time for maturation was also delayed at higher concentrations. In addition, locomotor behavior allowed for the discrimination of all tested chromium concentrations and the control group and from each other, proving to be the most sensitive endpoint. Overall, the data support the potential of T. longicaudatus as a model for ecotoxicity testing, using apical endpoints with impact at the population level; in particular, results suggest that behavior assessments in this species might be useful for detecting hazardous compounds in environmental monitoring of freshwater ecosystems.

The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of Chassalia curviflora (C. curviflora) in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length (P

IntroductionAutism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology.MethodsThe GABAB receptor agonist R-Baclofen and the selective agonist for the 5HT7 serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD. To evaluate the efficacy of these compounds in more details, we treated BTBR T+ Itpr3tf/J and B6.129P2-Fmr1tm1Cgr/J mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests.ResultsBTBR mice showed motor deficits, elevated anxiety, and highly repetitive behavior of self-grooming. Fmr1-KO mice exhibited decreased anxiety and hyperactivity. Additionally, Fmr1-KO mice’s ultrasonic vocalizations were impaired suggesting a reduced social interest and communication of this strain. Acute LP-211 administration did not affect the behavioral abnormalities observed in BTBR mice but improved repetitive behavior in Fmr1-KO mice and showed a trend to change anxiety of this strain. Acute R-Baclofen treatment improved repetitive behavior only in Fmr1-KO mice.ConclusionOur results add value to the current available data on these mouse models and the respective compounds. Yet, additional studies are needed to further test R-Baclofen and LP-211 as potential treatments for ASD therapy.

Naphthenic acids (NAs) are typical contaminants in heavily crude oil. Benzo[a]pyrene (B[a]P) is also a component of crude oil, but their combined effects have not been systematically explored. In this study, zebrafish (Danio rerio) were used as the test organisms, and behavioral indicators and enzyme activities were used as toxicity indicators. Combined with the effects of environmental concentrations, the toxic effects of low concentrations of commercially available NAs (0.5 mg/LNA) and benzo[a]pyrene (0.8 μg/LBaP) at single and compound exposures (0.5 mg/LNA and 0.8 μg/LBaP) were assayed in zebrafish, and transcriptome sequencing technology was used to explore the molecular mechanism of the two compounds affecting zebrafish from the molecular biology level. Sensitive molecular markers that could indicate the presence of contaminants were screened. The results showed that (1) zebrafish in the NA and BaP exposure groups exhibited increased locomotor behavior, and the mixed exposure group exhibited inhibition of locomotor behavior. Oxidative stress biomarkers showed increased activity under single exposure and decreased activity under the mixed exposure. (2) NA stress led to changes in the activity of transporters and the intensity of energy metabolism; BaP directly stimulates the pathway of actin production. When the two compounds are combined, the excitability of neurons in the central nervous system is decreased, and the actin-related genes are down-regulated. (3) After BaP and Mix treatments, genes were enriched in the cytokine-receptor interaction and actin signal pathway, while NA increased the toxic effect on the mixed treatment group. In general, the interaction between NA and BaP has a synergistic effect on the transcription of zebrafish nerve and motor behavior-related genes, resulting in increased toxicity under combined exposure. The changes in expression of various zebrafish genes are manifested in the changes in the normal movement behavior of zebrafish and the intensification of oxidative stress in the apparent behavior and physiological indicators. Capsule abstract: We investigated the toxicity and genetic alterations caused by NA, B[a]P, and their mixtures in zebrafish in an aquatic environment using transcriptome sequencing technology and comprehensive behavioral analysis. These changes involved energy metabolism, the generation of muscle cells, and the nervous system.

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.

This study aimed to investigate the antimigraine potential of quercetin in migraine pain induced by nitroglycerin (NTG), 10 mg/kg, intraperitoneal injection in rats. Quercetin was administered orally for 1 week, and behavioral parameters associated with pain were assessed 30 min after NTG injection. At the end of the study, the rats were killed so that immunohistochemical examination of their brains could be performed. The time and frequency of rearing and sniffing in the category of exploratory behavior, walking in the category of locomotor behavior, and total time spent in the light chamber were reduced in the disease control group compared with the normal group during the assessment of behavioral parameters. Pathologic migraine criteria, such as increased levels of calcitonin gene-related peptide and increased release of c-fos cells, were more prominent in the caudal nucleus triceminalis of the NTG control group. In the treatment groups, behavioral and pathological measures were less severe after pretreatment with quercetin at doses of 250 and 500 mg/kg. Therefore, it was concluded that quercetin improved the pain behavior of migraine patients in the NTG-induced migraine rat model. Quercetin is thought to have antimigraine effects due to its antioxidant and anti-inflammatory potential. Quercetin may therefore be a novel agent that can treat or prevent migraine pain and associated avoidance behaviors. [ABSTRACT FROM AUTHOR]

The femoral neck-shaft angle (NSA) can adapt to the early onset of habitual but changeable loading behaviors, such as sitting, crawling, standing, and cruising behaviors, and the adoption of immature through to mature walking patterns. However, normal patterns of skeletal growth can be modified by underlying pathological conditions. Femoral head depression and neck angulation can occur during vitamin D deficiency rickets, but the pattern of NSA deformation occurring during the period of locomotor development in children with rickets has not been widely studied. This study aimed to broaden understanding of rickets beyond historical and bioarchaeological prevalence rates to explore the functional impacts of the condition on femoral development. Radiographs of 200 children from eighteenth-to nineteenth-century London (76 rickets, 124 non-rickets) were measured for femoral NSA. The results demonstrate notable differences in NSA in children with and without rickets, which vary depending on disease status, severity, and age at onset. Children under 2 years with severe and marked cases of active rickets typically presented a higher femoral NSA, which may be attributed to delayed development during this disease phase and/or limited or delayed activity, potentially exacerbated by pain, muscle weakness, and childcare practices. In contrast, children over the age of 1 year with healed rickets frequently displayed femoral neck deformation and reduced NSA likely linked to mechanical loading experienced during the deficiency. Importantly, defects in the proximal femur can develop during recovery from poor mineralization and endochondral defects and may exaggerate the appearance of femoral neck deformation during continued growth. [ABSTRACT FROM AUTHOR]

Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug's side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic exposure in Drosophila melanogaster. Three-day-old flies were investigated into groups: Control, 0.001, 0.0025, 0.005, and 0.010 mg/mL of COL or NCCOL. The survival rate, open field test, LC50, oxidative stress markers (reactive species (RS) production, thiobarbituric acid reactive substances), antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase), protein thiols, nonprotein thiols, acetylcholinesterase activity, and cell viability were measured. As a result, acute exposure to the COL decreases the number of crosses in the open field and increases CAT activity. NCCOL reduced RS levels, increased lipoperoxidation and SOD activity. Chronic exposure to the COL and NCCOL in high concentrations implied high mortality and enzymatic inhibition of the CAT and AChE, and only the COL caused locomotor damage in the open field test. Thus, NCCOL again reduced the formation of RS while COL increased. In this comparative study, NCCOL was less toxic to the antioxidant system than COL and showed notable involvement of oxidative stress as one of their toxicity mechanisms. Future studies are needed to elucidate all aspects of nanosafety related to the NCCOL. Drug repositioning contributes to research involving emerging diseases. Nanoencapsulation of drugs aims to increase bioavailability. Certain concentrations of nanocolchicine affect Drosophila antioxidant enzymes. Oxidative stress pathways are involved in colchicine drug toxicity. The nanosafety of nanomaterials is essential for further research on a larger scale. [ABSTRACT FROM AUTHOR]

Simple Summary: Ocean noise pollution from marine traffic may affect the behavioral, ecological and biochemical parameters of marine fish species. Most studies have focused on behavioral changes and hearing damage in fishes, but the molecular mechanism of noise exposure in the impairment of the brain has rarely been reported. In this study, using small yellow croaker (L. polyactis) as a model, we used RNA-seq methods to characterize differently expressed genes between the control group and the noise exposure group. GO and KEGG pathway analysis found that synaptic transmission, neurotransmitter transport, endocytosis procession, cell adhesion molecules and the extracellular matrix receptor interaction pathway were over-represented in the DEGs. In addition, behavioral studies revealed that L. polyactis kept motionless on the surface of the water and lost the ability to keep their balance after noise exposure. Collectively, our results indicate that exposure to noise stressors contributes to neurological dysfunction in the brain and impaired locomotor ability in L. polyactis. Noise has the potential to induce physiological stress in marine fishes, which may lead to all sorts of ecological consequences. In the current study, we used the RNA-sequencing (RNA-seq) method to sequence the whole transcriptome of the brain in small yellow croaker (Larimichthys polyactis). The animals were exposed to a mix of noises produced by different types of boat played back in a tank, then the brain tissues were collected after the fish had been exposed to a 120 dB noise for 0.5 h. In total, 762 differently expressed genes (DEGs) between the two groups were identified, including 157 up regulated and 605 down regulated genes in the noise exposure group compared with the control group. Gene ontology (GO) enrichment analysis indicated that the most up regulated gene categories included synaptic membranes, receptor-mediated endocytosis and the neurotransmitter secretion process. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways found that endocytosis, cell adhesion molecules and the extracellular matrix (ECM) receptor interaction pathway were over-represented. Specifically, ECM-related genes, including lamin2, lamin3, lamin4, coll1a2, coll5a1 and col4a5 were down regulated in the noise exposure group, implying the impaired composition of the ECM. In addition, the behavioral experiment revealed that L. polyactis exhibited avoidance behaviors to run away from the noise source at the beginning of the noise exposure period. At the end of the noise exposure period, L. polyactis kept motionless on the surface of the water and lost the ability to keep their balance. Taken together, our results indicate that exposure to noise stress contributes to neurological dysfunction in the brain and impaired locomotor ability in L. polyactis. [ABSTRACT FROM AUTHOR]

Laboratory rodents spend the entire day housed in standard cages that provide a restricted area for movements and might, therefore, limit physical activity. However, it has not been tested in immature rodents of ages ranging from weaning to adulthood (adolescence period) whether the restricted area per animal does actually reduce physical activity and impact the body composition. We analyzed the spontaneous physical activity and feeding behavior during the adolescence of mice kept in two different housing conditions (standard stocking density (SSD) versus low stocking density (LSD)). We aimed to compare the body composition between SSD and LSD groups before they reached adulthood. Differential housing began at four weeks of age and was maintained for four weeks until euthanasia at eight weeks of age. The SSD group had a floor space of 88 cm2 available per animal, while LSD mice were housed with a floor space of 320 cm2 per animal, increasing the individual radius for movement more than three-fold compared with standard requirements. Mice kept in SSD exhibit lower spontaneous physical activity than mice kept in LSD. Early-life exposure to reduced physical activity in mice housed in SSD resulted in greater visceral fat accumulation before adulthood. An environment enabling/stimulating physical activity should be established for rodents as early as possible. This study will be helpful in showing that mice kept in SSD are early exposed to a reduced physical activity already in the adolescence period. Our findings could raise reflections about the translatability of rodents kept in SSD to healthy active humans. [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]

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus. [ABSTRACT FROM AUTHOR]

Selenium is an essential micronutrient derived from daily diet to maintain the normal growth and development of vertebrates. Excessive selenium intake will induce cardiovascular toxicity, reproductive toxicity and neurotoxicity. However, there have been few studies of the toxic effects of selenium on neural development and locomotor behavior. In this study, newly fertilized zebrafish embryos were treated with selenium. As a result, selenium treatment at the concentration of 0.5 µM decreased the moving speed and distance and blunted the touch response of zebrafish embryos. TUNEL assay and immunofluorescence analysis revealed that selenium induced nervous system impairment including promoted cell apoptosis, proliferation and neuroinflammation, and decreased neurons in zebrafish embryos. RNA-seq and RT-PCR results indicated that selenium treatment significantly decreased the expression of the dopaminergic neuron, motor neuron, GABAergic neuron and neurotransmitter transport marker genes in zebrafish embryos. The expression of PPAR signaling pathway marker genes was significantly down-regulated in selenium-treated embryos. Two PPAR agonists (rosiglitazone and bezafibrate) and an anti-cancer drug (cisplatin) were tested for their effects to alleviate selenium-induced locomotor defects. Rosiglitazone and bezafibrate could restore the expression of some neural marker genes but could not fully rescue the selenium-induced locomotor behavior defects. The supplementation of cisplatin could restore the dysfunctional locomotor behavior and the abnormal expression of the PPAR and neural marker genes to almost the normal levels. In conclusion, the results of this study reveal that selenium-induced neural development and locomotor behavior defects are caused by multiple complex factors including PPAR signaling, and all the factors might be recovered by cisplatin through unknown mechanisms.

The use of graphene and multi-walled carbon nanotubes (MWCNTs) has now become rather common in medical applications as well as several other areas thanks to their useful physicochemical properties. While in vitro testing offers some potential, in vivo research into toxic effects of graphene and MWCNTs could yield much more reliable data. Drosophila melanogaster has recently gained significant popularity as a dynamic eukaryotic model in examining toxicity, genotoxicity, and biological effects of exposure to nanomaterials, including oxidative stress, cellular immune response against two strains (NSRef and G486) of parasitoid wasp (Leptopilina boulardi), phenotypic variations, and locomotor behavior risks. D. melanogaster was used as a model organism in our study to identify the potential risks of exposure to graphene (thickness: 2-18 nm) and MWCNTs in different properties (as pure [OD: 10-20 nm short], modified by amide [NH2] [OD: 7-13 nm length: 55 μm], and modified by carboxyl [COOH] [OD: 30-50 nm and length: 0.5-2 μm]) at concentrations ranging from 0.1 to 250 μg/ml. Significant effects were observed at two high doses (100 and 250 μg/ml) of graphene or MWCNTs. This is the first study to report findings of cellular immune response against hematopoiesis and parasitoids, nanogenotoxicity, phenotypic variations, and locomotor behavior in D. melanogaster. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of Chassalia curviflora (C. curviflora) in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length (P<0.05) in studies on thiopental sodium-induced sleeping time at dosages of 100 and 200 mg/kg and a significant decrease (P<0.05) was found in terms of unconstrained locomotor and explorative activities in both hole crossing and open field tests at dosages of 100 and 200 mg/kg. Furthermore, the extracts increased sleeping time with a dosage-dependent onset of action. The hole-board test extracts also reduced the number of head dips at dosages of 100 and 200 mg/kg (P<0.05). It was found in this study that C. curviflora had the best neuropharmacological properties at a dosage of 200 ml/kg. Our findings also showed that all of the extracts from C. curviflora were experimentally active in an in vivo model. The study results suggested that the leaves had strong anti-depressant and hypnotic CNS properties that might be exploited for neuropharmacological adjuvant therapy in conventional medicine. However, pharmacological studies are warranted to explore the active substances and the mode of action. [ABSTRACT FROM AUTHOR]

This study deals with the impact of zinc on the locomotor activity rhythm of two terrestrial isopods Armadillo officinalis and Chetophiloscia elongata. Specimens are collected from the banks of Ghar El Melh lagoon. The locomotor rhythm of untreated and treated individuals with zinc is studied in the laboratory under constant darkness for 10 days. Results showed that untreated individuals of A. officinalis and C. elongata exhibited nocturnal behavior. After Zn exposure, these species concentrated their locomotor activities more or less in the subjective day. Whatever the species, the locomotor patterns became in majority multimodal for treated individuals. We noted, in addition, the absence of the unimodal profile. Through periodogram analysis, ultradian and circadian components were determined whatever the experimental conditions. The most important rhythmicity was determined in the control individual of A. officinalis (73.7%) as well as of C. elongata (52.6%). Furthermore, the locomotor behavior is less stable for contaminated individuals of the two sympatric species. Moreover, contrary to C. elongata, A. officinalis individuals became significantly more active after their exposure to zinc contaminated litter (αDD+Zn = 5h03 ± 2h33). [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is one of the most widely produced chemicals in the world used in the production of epoxy resins and polycarbonate plastics. BPA is easily migrated from the outer packaging to the contents. Due to the lipophilic property, BPA is easily accumulated in organisms. Perinatal low-dose BPA exposure alters brain neural development in later generations. In this study, after BPA treatment, the spontaneous movement of zebrafish larvae from the cleavage period to the segmentation period (1–24 hpf) was significantly decreased, with speed decreasing by 18.97% and distance decreasing between 18.4 and 29.7% compared to controls. Transcriptomics analysis showed that 131 genes were significantly differentially expressed in the exposed group during the 1–24 hpf period, among which 39 genes were significantly upregulated and 92 genes were significantly downregulated. The GO enrichment analysis, gene function analysis and real-time quantitative PCR of differentially expressed genes showed that the mRNA level of guanine deaminase (cypin) decreased significantly in the 1–24 hpf period. Moreover, during the 1–24 hpf period, BPA exposure reduced guanine deaminase activity. Therefore, we confirmed that cypin is a key sensitive gene for BPA during this period. Finally, the cypin mRNA microinjection verified that the cypin level of zebrafish larvae was restored, leading to the restoration of the locomotor activity. Taken together, the current results show that the sensitive period of BPA to zebrafish embryos is from the cleavage period to the segmentation period (1–24 hpf), and cypin is a potential target for BPA-induced neurodevelopmental toxicity. This study provides a potential sensitive period and a potential target for the deep understanding of neurodevelopmental toxicity mechanisms caused by BPA.

Parastar is an insecticide formulation of lambda-cyhalothrin and imidacloprid largely used for crop protection in North West Region of Cameroon. In the present study, we evaluated the behavioral activities and motor function of Wistar male rats after subchronic treatment with the pesticide formulation. To this end, three groups of adult rats were administered Parastar at doses 1.25, 2.49 and 6.23 mg/kg, respectively, for 35 days. A control group was included and received distilled water. At the end of the treatment, the animals were submitted to behavioral and functional tests (open field test, elevated plus maze test, light-dark box test, forced swimming test, tail suspension test, beam-walking test, grid suspension test and wire hang test) for estimation of anxiety, exploration, depression and motor coordination. Results revealed that Parastar, at the higher doses tested, 2.49 and 6.23 mg/kg, induced anxiogenic-like pattern behavior in rats in all behavioral assays including open field test (total distance moved, total lines crossed, frequency and total time in center square were all reduced), elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze), and light-dark box (the dark box duration increased, while light box duration time and frequency of transition between dark and light box decreased). Treatment with 2.49 and 6.23 mg/kg Parastar increased the immobility time of animals in both forced swimming test and tail suspension test. The insecticide induced decrease in the distance traveled, foot slip and number of turns of animals in the beam walking test. Parastar also decreased the animal suspension time in both grid suspension grip-strength test and the wire hang test. Taken altogether, these results suggest that subchronic administration of Parastar at the doses of 2.49 and 6.23 mg/kg induced anxiety-like and depressive-like behavior as well as impaired motor coordination and muscle strength in male rats. [ABSTRACT FROM AUTHOR]

Waterborne Benzo[a]pyrene (B[a]P) pollution is a global threat to aquatic organisms. The exposure to waterborne B[a]P can disrupt the normal locomotor behavior of zebrafish (Danio rerio), however, how it affect the locomotor behavior of adult zebrafish remains unclear. Herein, B[a]P at two concentrations (0.8 μg/L and 2.0 μg/L) were selected to investigate the molecular mechanisms of the affected locomotor behavior of zebrafish by B[a]P based on transcriptome profiling. Adverse effects of B[a]P exposure affecting locomotor behavior in zebrafish were studied by RNA sequencing, and the locomotion phenotype was acquired. The gene enrichment results showed that the differentially highly expressed genes (atp2a1, cdh2, aurka, fxyd1, clstn1, apoc1, mt-co1, tnnt3b, and fads2) of zebrafish are mainly enriched in adrenergic signaling in cardiomyocytes (dre04261) and locomotory behavior (GO:0007626). The movement trajectory plots showed an increase in the locomotor distance and velocity of zebrafish in the 0.8 μg/L group and the opposite in the 2.0 μg/L group. The results showed that B[a]P affects the variety of genes in zebrafish, including motor nerves, muscles, and energy supply, and ultimately leads to altered locomotor behavior.

Sulfometuron methyl (SM) is a widely used herbicide and thus leading to accumulation in the environment. The toxicity assessments of SM in model organisms are currently rare. In the present study, zebrafish were utilized for evaluating the detrimental effects of SM in aquatic vertebrates. Zebrafish embryos were exposed to 0, 10, 20, and 40 mg/L SM from 5.5 to 72 h post-fertilization (hpf), respectively. Consequently, SM exposure resulted in increasing the mortality rate and reducing hatching rate in larval zebrafish at 10, 20, and 40 mg/L SM-treated groups. The reduced numbers of immune cells (neutrophils and macrophages) were observed after SM exposure by a dose-dependent manner. The inflammatory responses (TLR4, MYD88, IL-1β, IL-6, IL-8, IFN-γ, IL-10, and TGF-β) were measured to estimate immune responses. Anti-inflammatory factors (IL-10 and TGF-β) were down-regulated in all the treated groups and significantly altered at 40 mg/L exposure group. Additionally, behavioral tests suggested that SM treatment significantly increased the total distance, average speed, and maximum acceleration of larval zebrafish during light-dark transition and subsequently enzymology test displayed the same trend to locomotor behaviors. The content significantly increased in oxidative stress, as reflected in ROS level in all the treated groups. The numbers of cell apoptosis were significantly increased at 20, and 40 mg/L and the highest concentration group induced the substantial increment (P

• 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]

Behavioral responses to trace metals (TM) in Armadillidium granulatum Brandt, 1833 collected from Sebkha El Ouafi were studied under controlled laboratory conditions. Avoidance test was conducted in individuals exposed to cadmium (Cd), lead (Pb) and zinc (Zn) during 48 hours. The locomotor activity was studied under entraining conditions (LD) and constant darkness (DD) in the control animals as well as those exposed to contaminated soil. Whatever the tested metal, the animals did not show avoidance behavior. The determined efficient concentration (EC50) was equal to 3.4 mg/L for Cd, 451 mg/L for Pb and 1043 mg/L for Zn. Furthermore, results revealed the existence of nocturnal behavior whatever the experimental conditions. Periodogram analysis showed the existence of ultradian and circadian periods. This last was globally longer for contaminated specimens than the control ones under entraining conditions as well as under constant darkness. Exposed animals to cadmium showed the most important activity time under DD (αDD = 8h01 ± 3h27) contrary to that observed under nLD cycle (αLD = 3h43 ± 2h36). In addition, control specimens and those exposed to Cd and Pb were characterized by a phase delay contrary to those exposed to Zn which showed a phase advance. [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]

Noise has the potential to induce physiological stress in marine fishes, which may lead to all sorts of ecological consequences. In the current study, we used the RNA-sequencing (RNA-seq) method to sequence the whole transcriptome of the brain in small yellow croaker (Larimichthys polyactis). The animals were exposed to a mix of noises produced by different types of boat played back in a tank, then the brain tissues were collected after the fish had been exposed to a 120 dB noise for 0.5 h. In total, 762 differently expressed genes (DEGs) between the two groups were identified, including 157 up regulated and 605 down regulated genes in the noise exposure group compared with the control group. Gene ontology (GO) enrichment analysis indicated that the most up regulated gene categories included synaptic membranes, receptor-mediated endocytosis and the neurotransmitter secretion process. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways found that endocytosis, cell adhesion molecules and the extracellular matrix (ECM) receptor interaction pathway were over-represented. Specifically, ECM-related genes, including lamin2, lamin3, lamin4, coll1a2, coll5a1 and col4a5 were down regulated in the noise exposure group, implying the impaired composition of the ECM. In addition, the behavioral experiment revealed that L. polyactis exhibited avoidance behaviors to run away from the noise source at the beginning of the noise exposure period. At the end of the noise exposure period, L. polyactis kept motionless on the surface of the water and lost the ability to keep their balance. Taken together, our results indicate that exposure to noise stress contributes to neurological dysfunction in the brain and impaired locomotor ability in L. polyactis.

Studies of circadian locomotor rhythms in Drosophila melanogaster gave evidence to the preceding theoretical predictions on circadian rhythms. The molecular oscillator in flies, as in virtually all organisms, operates using transcriptional-translational feedback loops together with intricate post-transcriptional processes. Approximately150 pacemaker neurons, each equipped with a molecular oscillator, form a circuit that functions as the central pacemaker for locomotor rhythms. Input and output pathways to and from the pacemaker circuit are dissected to the level of individual neurons. Pacemaker neurons consist of functionally diverse subclasses, including those designated as the Morning/Master (M)-oscillator essential for driving free-running locomotor rhythms in constant darkness and the Evening (E)-oscillator that drives evening activity. However, accumulating evidence challenges this dual-oscillator model for the circadian circuit organization and propose the view that multiple oscillators are coordinated through network interactions. Here we attempt to provide further evidence to the revised model of the circadian network. We demonstrate that the disruption of molecular clocks or neural output of the M-oscillator during adulthood dampens free-running behavior surprisingly slowly, whereas the disruption of both functions results in an immediate arrhythmia. Therefore, clocks and neural communication of the M-oscillator act additively to sustain rhythmic locomotor output. This phenomenon also suggests that M-oscillator can be a pacemaker or a downstream path that passively receives rhythmic inputs from another pacemaker and convey output signals. Our results support the distributed network model and highlight the remarkable resilience of the Drosophila circadian pacemaker circuit, which can alter its topology to maintain locomotor rhythms.

Paramyine ischyromyids are one of the first ancestral rodent groups to appear in North America. Studying ecological indicators of these extinct animals enables us to better understand how they integrated into North American mammalian communities. In this study we reassess the locomotor behavior of a nearly complete skeleton of a paramyine, Paramys delicatus (AMNH FM 12506), using functional limb indices and living squirrels as extant analogues. We then used the results of the functional limb index study to select an appropriate locomotor group for body mass estimations of Paramys delicatus and other early North American (Wasatchian-Bridgerian) paramyines. This was done because body mass is strongly tied to locomotor patterns and more reliable body mass estimates can be generated from an extant sample that functionally resembles the fossils being studied. Functional limb indices were calculated for three locomotor groups (arboreal, semifossorial, and gliding) of living sciurids. Comparisons among arboreal, semifossorial, and gliding sciurids show that the functional indices related to mechanical advantage of muscles and limb robusticity enable distinction among locomotor groups; however, there is considerable overlap between arboreal and semifossorial taxa. Paramys delicatus was found to have generally greater mechanical advantages and limb robusticity than most living squirrels, including semifossorial taxa. As these traits are associated with semifossorial squirrels that frequently use scratch-digging, this suggests that Paramys delicatus and perhaps other early paramyines were likely proficient scratch-diggers. However, indices reflecting limb proportions of paramyines suggest that these early rodents may have used more hind limb dominated locomotion than do living squirrels. Body mass estimations for early paramyines were therefore derived from a semifossorial squirrel sample. Statistical comparisons suggest that many of the most reliable estimators for body mass in Paramys delicatus and other paramyines are those derived from humeral dimensions, with the most reliable estimate being humeral head superoinferior breadth. Using these estimators, individual body mass estimates of early paramyines range from 3391 to 4005 g for Paramys delicatus, 1137–1329 g for Paramys copei, 1291 g for Paramys taurus, and 3357 g for Notoparamys costilloi. All body mass estimations derived from postcranial elements are substantially larger than previously published estimates derived from the dentition, which may be because postcranial elements play a larger role in supporting body weight. [ABSTRACT FROM AUTHOR]

Studies of circadian locomotor rhythms in Drosophila melanogaster gave evidence to the preceding theoretical predictions on circadian rhythms. The molecular oscillator in flies, as in virtually all organisms, operates using transcriptional-translational feedback loops together with intricate post-transcriptional processes. Approximately150 pacemaker neurons, each equipped with a molecular oscillator, form a circuit that functions as the central pacemaker for locomotor rhythms. Input and output pathways to and from the pacemaker circuit are dissected to the level of individual neurons. Pacemaker neurons consist of functionally diverse subclasses, including those designated as the Morning/Master (M)-oscillator essential for driving free-running locomotor rhythms in constant darkness and the Evening (E)-oscillator that drives evening activity. However, accumulating evidence challenges this dual-oscillator model for the circadian circuit organization and propose the view that multiple oscillators are coordinated through network interactions. Here we attempt to provide further evidence to the revised model of the circadian network. We demonstrate that the disruption of molecular clocks or neural output of the M-oscillator during adulthood dampens free-running behavior surprisingly slowly, whereas the disruption of both functions results in an immediate arrhythmia. Therefore, clocks and neural communication of the M-oscillator act additively to sustain rhythmic locomotor output. This phenomenon also suggests that M-oscillator can be a pacemaker or a downstream path that passively receives rhythmic inputs from another pacemaker and convey output signals. Our results support the distributed network model and highlight the remarkable resilience of the Drosophila circadian pacemaker circuit, which can alter its topology to maintain locomotor rhythms. [ABSTRACT FROM AUTHOR]

RNA-binding proteins play an important role in the regulation of post-transcriptional gene expression throughout the nervous system. This is underscored by the prevalence of mutations in genes encoding RNA splicing factors and other RNA-binding proteins in a number of neurodegenerative and neurodevelopmental disorders. The highly conserved alternative splicing factor Caper is widely expressed throughout the developing embryo and functions in the development of various sensory neural subtypes in the Drosophila peripheral nervous system. Here we find that caper dysfunction leads to aberrant neuromuscular junction morphogenesis, as well as aberrant locomotor behavior during larval and adult stages. Despite its widespread expression, our results indicate that caper function is required to a greater extent within the nervous system, as opposed to muscle, for neuromuscular junction development and for the regulation of adult locomotor behavior. Moreover, we find that Caper interacts with the RNA-binding protein Fmrp to regulate adult locomotor behavior. Finally, we show that caper dysfunction leads to various phenotypes that have both a sex and age bias, both of which are commonly seen in neurodegenerative disorders in humans. [Display omitted] • caper dysfunction results in aberrant neuromuscular junction morphogenesis. • caper is required for adult and larval locomotor behavior. • caper function has tissue specific requirements for neurogenesis and adult behavior. • caper interacts with Fmr1 to regulate adult locomotor behavior. • caper dysfunction results in age-dependent and sex-biased phenotypes. [ABSTRACT FROM AUTHOR]

Association to early mortality and sedentarism was already demonstrated in the literature; nevertheless, some possible biochemical mechanisms around physical inactivity still need answers. The use of an invertebrate model, such as Drosophila melanogaster, can reproduce reliable responses in inducing an exercise protocol with exogenous antioxidant supplementation. This study main evaluates the effect of exercise (EXE) associated with γ-oryzanol (ORY) supplementation to improve locomotor behavior, antioxidant defenses, and survival in Drosophila melanogaster. Two-day old flies were submitted to a protocol for seven days, divided into five groups: Control, Movement-Limited Flies (MLF), EXE, ORY [25 µM], and EXE + ORY [25 µM]. The survival rate was evaluated, followed by open field and negative geotaxis. Flies were euthanized and subjected to analysis for acetylcholinesterase (AChE) and antioxidant enzymes activity, glycidic and lipid parameters, body weight, reactive species (RS), and lipid peroxidation. EXE and EXE + ORY flies showed increased survival and locomotor activity, improved glycidic and lipid parameters, with a lower RS production, and increased antioxidant defenses compared to Control, and EXE + ORY when compared to the EXE group, obtained an increase in the ratio of protein levels/body weight, decreased ratio of triglyceride levels/body weight and decreased lipid peroxidation. However, MLF showed less survival and decreased locomotor activity, possibly due to increased AChE activity and reduced antioxidant defenses. The EXE and EXE + ORY demonstrate effective results in maintaining endogenous defenses, with increased locomotor activity, supporting evidence on EXE benefits, and supplementation with antioxidant compounds face of health paradigms. New protocol system of exercise on Drosophila melanogaster model. ORY demonstrates synergistic effect with EXE. Exercise with ORY supplementation increases locomotor behavior. Exercise with ORY supplementation decrease oxidative damages on flies. [ABSTRACT FROM AUTHOR]

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.

Abstract Background Galectins are a large family of proteins evolved to recognize specific carbohydrate moieties. Given the importance of pattern recognition processes for multiple biological tasks, including CNS development and immune recognition, we examined the home cage behavioral phenotype of mice lacking galectin-3 (Lgals3) function. Using a sophisticated monitoring apparatus capable of examining feeding, drinking, and movement at millisecond temporal and 0.5 cm spatial resolutions, we observed daily behavioral patterns from 10 wildtype male C57BL/6J and 10 Lgals3 constitutive knockout (Lgals3 −/−; both cohorts aged 2–3 months) mice over 17 consecutive days. We performed a second behavioral assessment of this cohort at age 6–7 months. Results At both ages, Lgals3 −/− mice demonstrated less movement compared to wildtype controls. Both forward locomotion and movement-in-place behaviors were decreased in Lgals3 −/− mice, due to decreased bout numbers, initiation rates, and durations. We additionally noted perturbation of behavioral circadian rhythms in Lgals3 −/− mice, with mice at both ages demonstrating greater variability in day-to-day performance of feeding, drinking, and movement (as assessed by Lomb-Scargle analysis) compared to wildtype. Conclusion Carbohydrate recognition tasks performed by Lgals3 may be required for appropriate development of CNS structures involved in the generation and control of locomotor behavior.

Controlling the environment of an organism has many biologically relevant applications. Temperature-dependent inducible biological reagents have proven invaluable for elucidating signaling cascades and dissection of neural circuits. Here we develop a simple and affordable system for rapidly changing temperature in a chamber housing adult Drosophila melanogaster. Utilizing flies expressing the temperature-inducible channel dTrpA1 in dopaminergic neurons we show rapid and reproducible changes in locomotor behavior. This device should have wide application to temperature-modulated biological reagents.