Changes In Locomotor Behavior Research Articles

MoS2 2D materials induce spinal cord neuroinflammation and neurotoxicity affecting locomotor performance in zebrafish.

MoS2 nanosheets belong to an emerging family of nanomaterials named bidimensional transition metal dichalcogenides (2D TMDCs). The use of such promising materials, featuring outstanding chemical and physical properties, is expected to increase in several fields of science and technology, with an enhanced risk of environmental dispersion and associated wildlife and human exposures. In this framework, the assessment of MoS2 nanosheets toxicity is instrumental to safe industrial developments. Currently, the impact of the nanomaterial on the nervous tissue is unexplored. In this work, we use as in vivo experimental model the early-stage zebrafish, to investigate whether mechano-chemically exfoliated MoS2 nanosheets reach and affect, when added in the behavioral ambient, the nervous system. By high throughput screening of zebrafish larvae locomotor behavioral changes upon exposure to MoS2 nanosheets and whole organism live imaging of spinal neuronal and glial cell calcium activity, we report that sub-acute and prolonged ambient exposures to MoS2 nanosheets elicit locomotor abnormalities, dependent on dose and observation time. While 25 μg mL-1 concentration treatments exerted transient effects, 50 μg mL-1 ones induced long-lasting changes, correlated to neuroinflammation-driven alterations in the spinal cord, such as astrogliosis, glial intracellular calcium dysregulation, neuronal hyperactivity and motor axons retraction. By combining integrated technological approaches to zebrafish, we described that MoS2 2D nanomaterials can reach, upon water (i.e. ambient) exposure, the nervous system of larvae, resulting in a direct neurological damage.

Transcriptome analysis reveals differences in developmental neurotoxicity mechanism of methyl-, ethyl-, and propyl- parabens in zebrafish embryos

Studies on the comparison of developmental (neuro) toxicity of parabens are currently limited, and unharmonized concentrations between phenotypic observations and transcriptome analysis hamper the understanding of their differential molecular mechanisms. Thus, developmental toxicity testing was conducted herein using the commonly used methyl- (MtP), ethyl- (EtP), and propyl-parabens (PrP) in zebrafish embryos. With a benchmark dose of 5%, embryonic-mortality-based point-of-departure (M-POD) values of the three parabens were determined, and changes in locomotor behavior were evaluated at concentrations of 0, M-POD/50, M-POD/10, and M-POD, where transcriptome analysis was conducted to explore the underlying neurotoxicity mechanism. Higher long-chained parabens were more toxic than short-chained parabens, as determined by the M-POD values of 154.1, 72.6, and 24.2 µM for MtP, EtP, and PrP, respectively. Meanwhile, exposure to EtP resulted in hyperactivity, whereas no behavioral effect was observed with MtP and PrP. Transcriptome analysis revealed that abnormal behaviors in the EtP-exposed group were associated with distinctly enriched pathways in signaling, transport, calcium ion binding, and metal binding. In contrast, exposure to MtP and PrP mainly disrupted membranes and transmembranes, which are closely linked to abnormal embryonic development rather than neurobehavioral changes. According to the changes in the expressions of signature mRNAs, tentative transcriptome-based POD values for each paraben were determined as MtP (2.68 µM), EtP (3.85 µM), and PrP (1.4 µM). This suggests that different molecular perturbations initiated at similar concentrations determined the extent and toxicity outcome differently. Our findings provide insight into better understanding the differential developmental neurotoxicity mechanisms of parabens.

Transcriptome profile of reserpine-induced locomotor behavioral changes in zebrafish (Danio rerio)

Reserpine is a drug that is commonly used as an antihypertensive and antipsychotic drug in clinical practice. During our previous research, we found that reserpine treatment in zebrafish larvae can cause depression-like behaviors, but the corresponding mechanisms are still unclear. In this study, we aimed to investigate the molecular mechanism by which reserpine exposure affects locomotor behaviors in larval zebrafish through transcriptome analysis. The gene enrichment results showed that the differentially highly expressed genes of zebrafish are mainly enriched in voltage-gated ion channels, dopaminergic synapses and wnt signaling pathways. Selected genes (apc2, cacna1aa, drd2b, dvl1a, fzd1, wnt1, wnt3a, wnt9a and wnt10a) by transcriptomic results was validated by real-time PCR. Consistently, Wnt signaling pathway inhibitor XAV939 may induce reduced behavioral changes in zebrafish larvae, while the Wnt signaling pathway agonist SB415286 reversed the reserpine-induced depressive effects. Our study provides gene transcriptional profile data for future research on reserpine-induced locomotor behavioral changes.

Documenting past South American camelid diversity at Telarmachay (Puna of Junín, Peru) using first phalanges morphometrics

To get insights into the elusive process of the domestication of South American Camelids (SAC), we focused on the Central Andean zone and the long sequence from Telarmachay (Puna of Junín, Peru), for which an early process of domestication, dating 5500-5000 BP, has been proposed. We explored the camelid diversity of Telarmachay with a morphometric approach using modern guanaco and vicuña first phalanges. Our results support the previous identification of both wild camelids and indicated hunting practices. They also suggest earlier camelid anthropic control based on the occurrence of intermediate sized specimens. However, Telarmachay camelids require further investigated using a more powerful approach to access reliable proxies of changes in locomotor behaviors.

Adverse effects of sulfamethoxazole on locomotor behavior and lipid metabolism by inhibiting acetylcholinesterase and lipase in Daphnia magna

Sulfamethoxazole (SMZ), a kind of sulfonamide antibiotic, is widely used in both human and veterinary medicine. Frequent detection of SMZ in natural aquatic environments has prompted growing attention and posed ecological risks to the ecosystem and human health. In this study, we investigated the ecotoxicological properties of SMZ upon Daphnia magna, and the mechanisms of the deleterious effects of SMZ were attempted to be elucidated by investigating a chain of parameters, including survival, reproduction, growth, locomotor behavior, metabolism, as well as levels of related enzyme activity and gene expression. After a 14-d sub-chronic exposure to SMZ at environmentally relevant concentrations, we observed virtually no lethal effect, weak growth inhibition, significant reproductive damage, evident ingestion rate decline, obvious change in locomotor behavior, and remarkable metabolic disorder. Notably, we identified SMZ as an inhibitor against acetylcholinesterase (AChE)/lipase in D. magna both in vivo and in vitro, which explained the adverse effects of SMZ on locomotor ability and lipid metabolism at the molecular levels. Furthermore, the direct interactions between SMZ and AChE/lipase were confirmed by using fluorescence spectrum and molecular docking. Together, our findings provide a new insight to advance the understanding of the environmental effects of SMZ on freshwater organisms.

Effect of Kisspeptin-Type Neuropeptide on Locomotor Behavior and Muscle Physiology in the Sea Cucumber Apostichopus japonicus.

Kisspeptins are neuropeptides encoded by the kiss1 gene, and little is known about them outside the vertebrate lineage. Two kisspeptin-type neuropeptides (KPs) have been discovered in Apostichopus japonicus (AjK1 and AjK2), an edible sea cucumber, and have been linked to reproductive and metabolic regulation. In this study, we evaluated how KPs affected locomotor behavior in one control group and two treatment groups (AjK1 and AjK2). We discovered that AjK1 had a significant dose effect, primarily by shortening the stride length and duration of movement to reduce the sea cucumber movement distance, whereas AjK2 had little inhibitory effect at the same dose. The levels of phosphatidylethanolamine (PE), phosphatidylcholine (PC), uridine, glycine, and L-serine in the longitudinal muscle of A. japonicus treated with AjK1 differed significantly from those of the control, which may explain the observed changes in locomotor behavior. Treatment with AjK2 induced changes in aspartate levels. Our results imply that AjK1 is more likely than AjK2 to have a role in the regulation of A. japonicus locomotion.

Intergenerational reproductive toxicity of parental exposure to prothioconazole and its metabolite on offspring and epigenetic regulation associated with DNA methylation in zebrafish

Prothioconazole (PTC) is a widely used agricultural fungicide, and its parent and metabolite prothioconazole-desthio (dPTC) have been detected in diverse environmental media. This study was aimed at investigating the gender-dependent effects on adult zebrafish reproduction and intergenerational effects on offspring development following parental exposure to PTC and dPTC. The results showed that after the adult zebrafish (F0) was exposed to 0.5 and 10 μg/L PTC and dPTC for 21 days, the fertility and gametogenesis of female zebrafish were decreased more significantly than that of male zebrafish. After that, three fecundity tests were conducted in the exposure period to explore the development endpoints of F1 embryos/larvae without further treatment with PTC and dPTC exposure. However, PTC and dPTC exposure did lead to abnormal development of F1 embryos, including delayed hatching, shortened body length, abnormal development and significant changes in locomotor behavior. These changes were related to the abnormal expression of sex hormones and the regulation of DNA methylation in F0 fish. In a word, the results of this study showed that parental PTC and dPTC interference have sex-dependent reproductive toxicity on F0 zebrafish, which may be passed on to the next generation through epigenetic modification involving DNA methylation, resulting in alternations in growth phenotype of offspring.

Behavioral and brain anatomical analysis of Foxg1 heterozygous mice.

FOXG1 Syndrome (FS) is a devastating neurodevelopmental disorder that is caused by a heterozygous loss-of-function (LOF) mutation of the FOXG1 gene, which encodes a transcriptional regulator important for telencephalic brain development. People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features. Current therapeutic approaches are entirely symptomatic, however the ability to rescue phenotypes in mouse models of other genetic neurodevelopmental disorders such as Rett syndrome, Angelman syndrome, and Phelan-McDermid syndrome by postnatal expression of gene products has led to hope that similar approaches could help modify the disease course in other neurodevelopmental disorders such as FS. While FoxG1 protein function plays a critical role in embryonic brain development, the ongoing adult expression of FoxG1 and behavioral phenotypes that present when FoxG1 function is removed postnatally provides support for opportunity for improvement with postnatal treatment. Here we generated a new mouse allele of Foxg1 that disrupts protein expression and characterized the behavioral and structural brain phenotypes in heterozygous mutant animals. These mutant animals display changes in locomotor behavior, gait, anxiety, social interaction, aggression, and learning and memory compared to littermate controls. Additionally, they have structural brain abnormalities reminiscent of people with FS. This information provides a framework for future studies to evaluate the potential for post-natal expression of FoxG1 to modify the disease course in this severe neurodevelopmental disorder.

Establishing the Molecular and Functional Diversity of Spinal Motoneurons.

Spinal motoneurons are a remarkably diverse class of neurons responsible for facilitating a broad range of motor behaviors and autonomic functions. Studies of motoneuron differentiation have provided fundamental insights into the developmental mechanisms of neuronal diversification, and have illuminated principles of neural fate specification that operate throughout the central nervous system. Because of their relative anatomical simplicity and accessibility, motoneurons have provided a tractable model system to address multiple facets of neural development, including early patterning, neuronal migration, axon guidance, and synaptic specificity. Beyond their roles in providing direct communication between central circuits and muscle, recent studies have revealed that motoneuron subtype-specific programs also play important roles in determining the central connectivity and function of motor circuits. Cross-species comparative analyses have provided novel insights into how evolutionary changes in subtype specification programs may have contributed to adaptive changes in locomotor behaviors. This chapter focusses on the gene regulatory networks governing spinal motoneuron specification, and how studies of spinal motoneurons have informed our understanding of the basic mechanisms of neuronal specification and spinal circuit assembly.

Decabromodiphenyl Ethane Mainly Affected the Muscle Contraction and Reproductive Endocrine System in Female Adult Zebrafish.

The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a widespread environmental pollutant. However, the target tissue and toxicity of DBDPE are still not clear. In the current study, female zebrafish were exposed to 1 and 100 nM DBDPE for 28 days. Chemical analysis revealed that DBDPE tended to accumulate in the brain other than the liver and gonad. Subsequently, tandem mass tag-based quantitative proteomics and parallel reaction monitoring verification were performed to screen the differentially expressed proteins in the brain. Bioinformatics analysis revealed that DBDPE mainly affected the biological process related to muscle contraction and estrogenic response. Therefore, the neurotoxicity and reproductive disruptions were validated via multilevel toxicological endpoints. Specifically, locomotor behavioral changes proved the potency of neurotoxicity, which may be caused by disturbance of muscular proteins and calcium homeostasis; decreases of sex hormone levels and transcriptional changes of genes related to the hypothalamic-pituitary-gonad-liver axis confirmed reproductive disruptions upon DBDPE exposure. In summary, our results suggested that DBDPE primarily accumulated in the brain and evoked neurotoxicity and reproductive disruptions in female zebrafish. These findings can provide important clues for a further mechanism study and risk assessment of DBDPE.

Impact of selection and domestication on hindlimb bones of modern reindeer populations: Archaeological implications for early reindeer management by Sámi in Fennoscandia

ABSTRACT For centuries, reindeer herding has been an integral part of the subsistence and culture among the Sámi of northern Fennoscandia. Despite the importance of this husbandry in their history, the timing and details of early reindeer domestication are still highly debated. Indeed, identifying domesticated individuals in the archaeological record remains complicated because reindeer are still considered to be in the early phases of the domestication process. In this work, we propose solutions for identifying domestic individuals using 3D geometric morphometrics on isolated elements from the long bones of the hindlimb in modern reindeer populations. These bones are important for understanding both the mobility of reindeer and the effect of load carrying or draught. A good level of distinction between the size and shape variables of these bones was found among subspecies, sex and lifestyles. This demonstrates that the long bones of the hindlimb can provide information on changes in locomotor behaviour induced by the domestication process, such as control and reduction of reindeer mobility by humans. This also demonstrates that analysis in geometric morphometrics is useful for exploring the use of draught reindeer in early Sámi reindeer herding and the implications for understanding reindeer domestication and early reindeer herding strategies.

Investigating the impact of captivity and domestication on limb bone cortical morphology: an experimental approach using a wild boar model

The lack of bone morphological markers associated with the human control of wild animals has prevented the documentation of incipient animal domestication in archaeology. Here, we assess whether direct environmental changes (i.e. mobility reduction) could immediately affect ontogenetic changes in long bone structure, providing a skeletal marker of early domestication. We relied on a wild boar experimental model, analysing 24 wild-born specimens raised in captivity from 6 months to 2 years old. The shaft cortical thickness of their humerus was measured using a 3D morphometric mapping approach and compared with 23 free-ranging wild boars and 22 pigs from different breeds, taking into account sex, mass and muscle force differences. In wild boars we found that captivity induced an increase in cortical bone volume and muscle force, and a topographic change of cortical thickness associated with muscular expression along a phenotypic trajectory that differed from the divergence induced by selective breeding. These results provide an experimental proof of concept that changes in locomotor behaviour and selective breeding might be inferred from long bones morphology in the fossil and archaeological record. These trends need to be explored in the archaeological record and further studies are required to explore the developmental changes behind these plastic responses.

Effects of state anxiety on gait: a 7.5% carbon dioxide challenge study

We used the 7.5% carbon dioxide (CO2) model of anxiety induction to investigate the effects of state anxiety on normal gait and gait when navigating an obstacle. Healthy volunteers (n = 22) completed a walking task during inhalations of 7.5% CO2 and medical air (placebo) in a within-subjects design. The order of inhalation was counterbalanced across participants and the gas was administered double-blind. Over a series of trials, participants walked the length of the laboratory, with each trial requiring participants to navigate through an aperture (width adjusted to participant size), with gait parameters measured via a motion capture system. The main findings were that walking speed was slower, but the adjustment in body orientation was greater, during 7.5% CO2 inhalation compared to air. These findings indicate changes in locomotor behaviour during heightened state anxiety that may reflect greater caution when moving in an agitated state. Advances in sensing technology offer the opportunity to monitor locomotor behaviour, and these findings suggest that in doing so, we may be able to infer emotional states from movement in naturalistic settings.

Developmental exposure of zebrafish to vitamin D receptor acting drugs and environmental toxicants disrupts behavioral function

Vitamin D receptor (VDR) signaling is important for optimal neurobehavioral development. Disruption of VDR signaling by environmental toxicants during early development might contribute to the etiology of behavioral dysfunction. In the current set of studies, we examined ten compounds known to affect VDR function in vitro for neurobehavioral effects in vivo in zebrafish. Zebrafish embryos were exposed to concentrations of the compounds in their water during the first 5 days post-fertilization. On day 5, the embryos were tested in an alternating light-dark locomotor assay using a computerized video tracking system. We found that most of the compounds produced significant changes in locomotor behavior in exposed zebrafish larvae, although the direction of the effect (i.e., hypo- or hyperactivity) and the sensitivity of the effect to changes in illumination condition varied across the compounds. The nature of the behavioral effects generally corresponded to the effects these compounds have been shown to exert on VDR. These studies lay a foundation for further investigation to determine whether behavioral dysfunction persists into adulthood and if so which behavioral functions are affected. Zebrafish can be useful for screening compounds identified in high throughput in vitro assays to provide an initial test for how those compounds would affect construction and behavioral function of a complex nervous system, helping to bridge the gap between in vitro neurotoxicity assays and mammalian models for risk assessment in humans.

Optimizing clozapine for chemogenetic neuromodulation of somatosensory cortex

Clozapine (CLZ) has been proposed as an agonist for Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), to replace Clozapine-N-oxide (CNO); however, there are no reliable guidelines for the use of CLZ for chemogenetic neuromodulation. We titrated the optimal dose of CLZ required to evoke changes in neural activity whilst avoiding off-target effects. We also performed [18F]Fluoro-deoxy-glucose micro positron emission tomography (FDG-microPET) scans to determine the global effect of CLZ-induced hM3D(Gq) DREADD activation in the rat brain. Our results show that low doses of CLZ (0.1 and 0.01 mg/kg) successfully induced neural responses without off-target effects. CLZ at 1 mg/kg evoked a stronger and longer-lasting neural response but produced off-target effects, observed as changes in locomotor behavior and FDG-microPET imaging. Unexpectedly, FDG-microPET imaging failed to demonstrate an increase in regional glucose metabolism in the stimulated cortex during CLZ chemogenetic neuromodulation. Therefore, caution should be used when interpreting FDG-PET images in the context of cortical chemogenetic activation.

The mark of captivity: plastic responses in the ankle bone of a wild ungulate (Sus scrofa).

Deciphering the plastic (non-heritable) changes induced by human control over wild animals in the archaeological record is challenging. We hypothesized that changes in locomotor behaviour in a wild ungulate due to mobility control could be quantified in the bone anatomy. To test this, we experimented with the effect of mobility reduction on the skeleton of wild boar (Sus scrofa), using the calcaneus shape as a possible phenotypic marker. We first assessed differences in shape variation and covariation in captive-reared and wild-caught wild boars, taking into account differences in sex, body mass, available space for movement and muscle force. This plastic signal was then contrasted with the phenotypic changes induced by selective breeding in domestic pigs. We found that mobility reduction induces a plastic response beyond the shape variation of wild boars in their natural habitat, associated with a reduction in the range of locomotor behaviours and muscle loads. This plastic signal of captivity in the calcaneus shape differs from the main changes induced by selective breeding for larger muscle and earlier development that impacted the pigs' calcaneus shape in a much greater extent than the mobility reduction during the domestication process of their wild ancestors.

Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency.

Disrupted-in-Schizophrenia 1 (DISC1) is a susceptibility gene for several psychiatric illnesses. To study the pathogenesis of these disorders, we generated Disc1 mutant mice by introducing the 129S6/SvEv 25-bp deletion Disc1 variants into the C57BL/6J strain. In this study, we used heterozygous Disc1 mutant (Het) mice to evaluate the DISC1 haploinsufficiency model of schizophrenia. No changes in locomotor behaviors were observed in Het mice; however, after amphetamine injection, greater locomotor activity was observed in Het mice compared with wild-type (WT) mice. Moreover, amphetamine-induced elevations of c-Fos expression and dopamine level in the striatum were greater in Het mice than in WT controls, suggesting an altered dopaminergic regulation in the striatum of Het mice. Compared with those in WTs, the striatal protein levels of dopamine transporter and D2 dopamine receptor were increased in Het mice, while D1 dopamine receptor level was decreased. DISC1 interacting proteins, GSK3α and GSK3β, were downregulated in Het mice, whereas the levels of PDE4B and CREB were not altered. Morphologically, the complexities of striatal median spiny neurons (MSNs), parvalbumin-positive interneurons and Iba1-positive microglia were all decreased in Het mice. The density and head diameter of dendritic spines in the MSNs of Het mice were also reduced. Our results indicate that mice lacking one WT Disc1 allele are more sensitive to psychostimulant amphetamine challenge, which might be attributed to the altered structure and function of the striatal dopaminergic system. Here, we demonstrated striatal phenotypes in heterozygous Disc1 mutant mice, which could be a promising model of DISC1 haploinsufficiency.

An inexpensive air stream temperature controller and its use to facilitate temperature-controlled behavior in Drosophila.

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.

A recreational dose of methylphenidate, but not methamphetamine, decreases anxiety-like behavior in female rats

Methylphenidate (MPH) and methamphetamine (METH) are two commonly abused psychomotor stimulants that impact anxiety, but in a manner that is currently unclear. This study adds to the literature by testing the effects of MPH and METH on anxiety in adult female rats, which has not previously been studied. In Experiment1, changes in anxiety-like behavior were determined using the Elevated Plus Maze (EPM) following either an acute injection of saline, METH (1 mg/kg), or MPH (10 mg/kg). Changes in general locomotion were measured using the open field test. MPH, but not METH, significantly decreased anxiety; MPH and METH were associated with increased activity in the open field. In Experiment2, we compared the effects of three once daily injections of saline to MPH (10 mg/kg) or METH (1 mg/kg). As with the acute dosing, repeated exposure to MPH, but not METH, decreased anxiety, and both drugs increased locomotion. Neither acute nor chronic dosing produced a change in locomotion during the EPM, indicating that the anxiolytic effects of MPH are independent of changes in locomotor behavior. These findings add further clarification to the literature investigating the psychoactive properties of MPH, with a special and needed emphasis on female behavior.

Bifenthrin causes transcriptomic alterations in mTOR and ryanodine receptor-dependent signaling and delayed hyperactivity in developing zebrafish (Danio rerio)

Over the last few decades, the pyrethroid insecticide bifenthrin has been increasingly employed for pest control in urban and agricultural areas, putting humans and wildlife at increased risk of exposure. Exposures to nanomolar (nM) concentrations of bifenthrin have recently been reported to alter calcium oscillations in rodent neurons. Neuronal calcium oscillations are influenced by ryanodine receptor (RyR) activity, which modulates calcium-dependent signaling cascades, including the mechanistic target of rapamycin (mTOR) signaling pathway. RyR activity and mTOR signaling play critical roles in regulating neurodevelopmental processes. However, whether environmentally relevant levels of bifenthrin alter RyR or mTOR signaling pathways to influence neurodevelopment has not been addressed. Therefore, our main objectives in this study were to examine the transcriptomic responses of genes involved in RyR and mTOR signaling pathways in zebrafish (Danio rerio) exposed to low (ng/L) concentrations of bifenthrin, and to assess the potential functional consequences by measuring locomotor responses to external stimuli. Wildtype zebrafish were exposed for 1, 3 and 5 days to 1, 10 and 50 ng/L bifenthrin, followed by a 14 d recovery period. Bifenthrin elicited significant concentration-dependent transcriptional responses in the majority of genes examined in both signaling cascades, and at all time points examined during the acute exposure period (1, 3, and 5 days post fertilization; dpf), and at the post recovery assessment time point (19 dpf). Changes in locomotor behavior were not evident during the acute exposure period, but were observed at 19 dpf, with main effects (increased locomotor behavior) detected in fish exposed developmentally to bifenthrin at 1 or 10 ng/L, but not 50 ng/L. These findings illustrate significant influences of developmental exposures to low (ng/L) concentrations of bifenthrin on neurodevelopmental processes in zebrafish.