Search Results (67)

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Hyperekplexia (OMIM 149400), a sensorimotor syndrome of perinatal clinical relevance, causes newborns to display an energic startle reflex in response to certain trivial stimuli. This condition can be lethal due to apnea episodes. The disease is caused by a blockade of glycinergic neurotransmission. Glycinergic interneurons preserve their identity by the activity of the surface glycine transporter GlyT2, which supplies glycine to presynaptic terminals to maintain glycine content in synaptic vesicles. Loss-of-function mutations in the GlyT2 gene (SLC6A5) cause a presynaptic form of human hyperekplexia. Here, we describe a new GlyT2 variant found in an infantile patient diagnosed with hyperekplexia. A missense mutation in the open reading frame of the GlyT2 gene inherited in homozygosity caused the substitution G449E in a residue highly conserved across the phylogenetic scale. The sequences of the glycine receptor genes GLRA1 and GLRB did not show abnormalities. We expressed the recombinant GlyT2 variant in heterologous cells and analyzed its pathogenic mechanism. The transporter was totally inactive, behaving as a bona fide loss-of-function mutant. Furthermore, the mutation promoted the abnormal insertion of the protein into the membrane, leading to its large incorporation into lipid rafts. However, there was no apparent alteration of wild-type trafficking upon mutant coexpression, as the mutant was prematurely degraded from the endoplasmic reticulum. Rescue with chemical chaperones was not possible for this mutant. Proteomics demonstrated that the expression of the mutant induced the unfolded protein response and interfered with raft-dependent processes. Therefore, the new variant causes a loss of function regarding GlyT2 activity but a gain of function as a cell proteostasis disturber. Full article

A single intratympanic application of the small-molecule drug AC102 was previously shown to promote significant recovery of hearing thresholds in a noise-induced hearing loss model in guinea pigs. Here, we report the effects of AC102 to revert synaptopathy of inner hair cells (IHCs) and behavioral signs of tinnitus in Mongolian gerbils following mild noise trauma. This experimental protocol led to minor hearing threshold shifts with no loss of auditory hair cells (HCs) but induced synaptopathy and a sustained and significant tinnitus percept. Treatment by intratympanic application of AC102 was evaluated in two protocols: 1. three weekly injections or 2. a single application. We evaluated hearing threshold changes using the auditory brainstem response (ABR) and the development of a tinnitus percept using the gap prepulse inhibition of acoustic startle (GPIAS) behavioral response. The number of IHC ribbon synapses along the cochlear frequency map were counted by immunostaining for the synaptic ribbon protein carboxy-terminal binding protein 2 (CTBP2). AC102 strongly and significantly reduced behavioral signs of tinnitus, as reflected by altered GPIAS. Noise-induced loss of IHC ribbon synapses was significantly reduced by AC102 compared to vehicle-treated ears. These results demonstrate that a single application of AC102 restores ribbon synapses following mild noise trauma thereby promoting recovery from tinnitus-related behavioral responses in vivo. Full article

Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Adult zebrafish received a single intraperitoneal (i.p.) injection of ACR (800 μg/g), followed by AD4 (400 μg/g i.p.) or PBS 24 h later. ACR exposure reduced brain GSH levels by 51% reduction at 48 h, an effect fully reversed by AD4 treatment. Behavioral analyses showed that AD4 rescued ACR-induced deficits in short-term habituation of the acoustic startle response (ASR). Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These results demonstrate AD4’s neuroprotective effects against acute ACR-induced brain toxicity, highlighting its therapeutic potential and validating adult zebrafish as a translational model for studying neurotoxic mechanisms and neuroprotective interventions. Full article

The inner ear and/or lateral line are responsible for hearing and balance of vertebrate. The otic sensory hair cells (HCs) employ cilium organelles, namely stereocilia and/or kinocilia, to mediate mechanical stimuli to electrical signal transition. Tektins (Tekts) are known as the cilium microtubule stabilizer and inner-space filler, and four Tekt(1-4)-encoding genes are identified in zebrafish HCs, but the subcellular location of Tekts in HCs remains unknown. In the present study, we first found that tekt3 is expressed in the inner ear and lateral line neuromast. Antibody staining revealed that Tekt3 is present in neuromast and utricular HCs. It is absent in the saccule, the authentic hearing end-organ of zebrafish and the crista of semi-circular canals. Furthermore, Tekt3 were enriched at the apical side of neuromast and utricular HCs, mainly in the cytosol. Similar subcellular distribution of Tekt3 was also evident in the outer HCs of mature mouse cochlea, which are not directly linked to the hearing sense. However, only neuromast HCs exerted morphological defect of kinocilia in tekt3 mutant. The disrupted or distorted HC kinocilia of mutant neuromast ultimately resulted in slower vital dye intake, delayed HC regeneration after neomycin treatment, and reduced startle response to vibration stimulation. All functional defects of tekt3 mutant were largely rescued by wild-type tekt3 mRNA. Our study thus suggests that zebrafish Tekt3 maintains the integrity and function of neuromast kinocilia to against surrounding and persistent low-frequency noises, perhaps via the intracellular distribution of Tekt3. Nevertheless, TEKT3/Tekt3 could be used to clarify HC sub-types in both zebrafish and mice, to highlight the non-hearing HCs. Full article

While automated-driving technology is advancing rapidly, human-centered research is still in its early stages. Research on negative user responses to automated driving is particularly limited in complex roadway environments such as roundabouts, where driving decisions typically depend on driver judgment and traffic conditions. In these environments, automated-driving vehicles may exhibit unstable behaviors, such as sudden stops or forced intersection entries. Since successful interaction between users and automated systems is critical for widespread adoption, understanding when and how automated driving negatively affects users is essential. This study investigated user psychological responses and corresponding physiological changes during unstable automated-driving situations. Using a virtual environment driving simulator, we compared two scenarios: sensor-only automated driving (A.D(S)), which exhibited unstable driving patterns; and cooperative automated driving (A.D(C)), which achieved more stable performance through infrastructure communication. We analyzed the responses of 30 participants using electromyography (EMG) measurements and pupil diameter tracking, supplemented by qualitative evaluations. Results showed that A.D(S) participants experienced higher levels of frustration during prolonged waiting times compared to A.D(C) participants. In addition, sudden braking events elicited startle responses characterized by pupil dilation and elevated arm-muscle EMG readings. This research advances our understanding of how automated-driving behaviors affect user experience and emphasizes the importance of human factors in the development of automated-driving technologies. Full article

Background: Sensory modulation may play a significant role in psychiatric conditions, including anxiety, and explain arousability levels, behavioral disorders, and functional deficits. Yet, studies about sensory modulation in adolescents with anxiety disorders are scarce. Purpose: To profile the prevalence of sensory modulation difficulties (SMDs) in adolescents with anxiety and examine their relations to arousability and psychopathology. The study compared adolescents with anxiety disorders to healthy controls using physiological measures and self-reports that reflect daily life scenarios. Then, the study examined the relationship between SMDs, arousability, and psychopathological severity in the study group. Method: Participants were 106 adolescents, aged 10.5–18 years and their parents. The study group included 44 participants diagnosed with anxiety disorder by psychiatrists. The control group included 62 healthy participants matched by age and gender to the study group. Parents completed the demographic questionnaire and the Child Behavior Checklist (CBCL). The adolescents completed The Revised Children’s Manifest Anxiety Scale (RCMAS) and the Adolescent/Adult Sensory Profile (AASP) and underwent the electrodermal activity (EDA) and pulse rate tests while listening to extreme sensory stimuli of auditory startles. Results: Based on AASP, the study group had a higher prevalence of SMDs expressed in lower sensory seeking, difficulties in registering sensory stimuli, and higher sensory sensitivity and avoidance. The study group presented higher arousability while listening to the startles as manifested in higher heart rate and EDA responses. The physiological results correlated with SMD levels measured by the AASP self-reports. SMDs correlated with psychopathological severity. Conclusions: SMDs may characterize adolescents with anxiety disorders and impact their arousability, symptoms severity, and daily functioning. Therefore, sensory modulation should be evaluated using both self-reports (to reflect implications in real life from patients’ own voices) along with objective measures to explain daily behaviors by underlying physiological mechanisms. This may focus intervention towards better health, function, and development. Full article

Background: Cholera is a diarrheal disease prevalent in populations without access to clean water. Cholera is caused by Vibrio cholerae, which colonizes the upper small intestine in humans once ingested. A growing number of studies suggest that the gut microbiome composition modulates animal behavior. Zebrafish are an established cholera model that can maintain a complex, mature gut microbiome during infection. Larval zebrafish, which have immature gut microbiomes, provide the advantage of high-throughput analyses for established behavioral models. Methods: We identified the effects of V. cholerae O1 El Tor C6706 colonization at 5 days post-fertilization (dpf) on larval zebrafish behavior by tracking startle responses at 10 dpf. We also characterized the larval gut microbiome using 16S rRNA sequencing. V. cholerae-infected or uninfected control groups were exposed to either an alternating light/dark stimuli or a single-tap stimulus, and average distance and velocity were tracked. Results: While there was no significant difference in the light/dark trial, we report a significant decrease in distance moved for C6706-colonized larvae during the single-tap trial. Conclusion: This suggests that early V. cholerae colonization of the larval gut microbiome has a dampening effect on sensorimotor function, supporting the idea of a link between the gut microbiome and behavior. Full article

The lateral line system in fish is crucial for detecting water flow, which facilitates various behaviors such as prey detection, predator avoidance, and rheotaxis. The cupula, a gelatinous structure overlaying the hair cells in neuromasts, plays a key role in transmitting mechanical stimuli to hair cells. However, the molecular composition of the cupula matrix remains poorly understood. In this study, we found that Mucin-5AC, a novel family of mucin proteins, composed of 2–27 cysteine-rich domains, presents in cartilaginous and bony fishes. Using in situ hybridization and transgenic reporter assays, we demonstrated that zebrafish muc5AC is specifically expressed in the support cells of neuromasts. Knockdown of muc5AC via antisense morpholino resulted in shorter cupulae in zebrafish lateral line. Additionally, we generated zebrafish muc5AC mutants using CRISPR/Cas9 and found that cupulae in muc5AC mutants were significantly shorter than that in wild-types, but the hair cell number in neuromasts was not changed obviously. Furthermore, muc5AC mutant zebrafish larvae displayed compromised sensitivity to vibration stimuli compared to wild-type larvae. This study provides the first evidence linking the muc5AC gene to cupula development and vibration detection in zebrafish. Our findings suggest that Mucin-5AC is likely a critical component of the cupula matrix, offering an important clue to the molecular composition of the lateral line cupula in fish. Full article

Background: Canine behavior plays an important role in the success of the human–dog relationship and the dog’s overall welfare, making selection for behavior a vital part of any breeding program. While behaviors are complex traits determined by gene × environment interactions, genetic selection for desirable behavioral phenotypes remains possible. Methods: No genomic association studies of dog behavior to date have been reported on a commercial breeding (CB) cohort; therefore, we utilized dogs from these facilities (n = 615 dogs). Behavioral testing followed previously validated protocols, resulting in three phenotypes/variables [social fear (SF), non-social fear (NSF), and startle response (SR)]. Dogs were genotyped on the 710 K Affymetrix Axiom CanineHD SNP array. Results: Inbreeding coefficients indicated that dogs from CB facilities are statistically less inbred than dogs originating from other breeding sources. Heritability estimates for behavioral phenotypes ranged from 0.042 ± 0.045 to 0.354 ± 0.111. A genome-wide association analysis identified genetic loci associated with SF, NSF, and SR; genes near many of these loci have been previously associated with behavioral phenotypes in other populations of dogs. Finally, genetic risk scores demonstrated differences between dogs that were more or less fearful in response to test stimuli, suggesting that these behaviors could be subjected to genetic improvement. Conclusions: This study confirms several canine genetic behavioral loci identified in previous studies. It also demonstrates that inbreeding coefficients of dogs in CB facilities are typically lower than those in dogs originating from other breeding sources. SF and NSF were more heritable than SR. Risk allele and weighted risk scores suggest that fearful behaviors could be subjected to genetic improvement. Full article

Thyroid hormones (THs) require iodine for biosynthesis and play critical roles in brain development. Perchlorate is an environmental contaminant that reduces serum THs by blocking the uptake of iodine from the blood to the thyroid gland. Using a pregnant rodent model, we examined the impact of maternal exposure to perchlorate under conditions of dietary iodine deficiency (ID) on the brain and behavior of offspring. We observed modest reductions in thyroxine (T4) in the serum of dams and no effect on T4 in pup serum in response to maternal exposure to 300 ppm of perchlorate in the drinking water. Likewise, serum T4 was reduced in ID dams, but, as with perchlorate, no effects were evident in the pup. However, when ID was coupled with perchlorate, reductions in pup serum THs and transcriptional alterations in the thyroid gland and pup brain were detected. These observations were accompanied by reductions in the number of cortical inhibitory interneurons containing the calcium-binding protein parvalbumin (Pvalb). Alterations in Pvalb expression in the neonatal brain were associated with deficits in the prepulse inhibition of acoustic startle in adult male offspring and enhanced fear conditioning in females. These findings support and extend structural defects in the brain previously reported in this model. Further, they underscore the critical need to consider additional non-chemical stressors in the determination of hazards and risks posed by environmental contaminants that affect the thyroid system. Full article

Background/Objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7-O-methylvestitol. Methods: BFRP’s toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract’s effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP’s main compounds. Results: BFRP primarily contained vestitol (128.24 ± 1.01 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP. Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties. Full article

The sensorimotor gating is a nervous system function that modulates the acoustic startle response (ASR). Prepulse inhibition (PPI) phenomenon is an operational measure of sensorimotor gating, defined as the reduction of ASR when a high intensity sound (pulse) is preceded in milliseconds by a weaker stimulus (prepulse). Brainstem nuclei are associated with the mediation of ASR and PPI, whereas cortical and subcortical regions are associated with their modulation. However, it is still unclear how the modulatory units can influence PPI. In the present work, we developed a computational model of a neural circuit involved in the mediation (brainstem units) and modulation (cortical and subcortical units) of ASR and PPI. The activities of all units were modeled by the leaky-integrator formalism for neural population. The model reproduces basic features of PPI observed in experiments, such as the effects of changes in interstimulus interval, prepulse intensity, and habituation of ASR. The simulation of GABAergic and dopaminergic drugs impaired PPI by their effects over subcortical units activity. The results show that subcortical units constitute a central hub for PPI modulation. The presented computational model offers a valuable tool to investigate the neurobiology associated with disorder-related impairments in PPI. Full article

Millions of hatchery-reared Rainbow trout are currently released in Australian waters to support recreational fisheries objectives, yet many of these fish die soon after release. In addition, little is known whether these fish harbour parasites that can potentially threaten freshwater ecosystems and human health. Here, we tested the behaviour of hatchery-reared trout using six tank-based tests at six different ages to evaluate their chances of survival and then dissected fish to investigate parasite prevalence. At 7 weeks of age fish readily emerged from a hide and showed the greatest number of startle responses to predators. Behaviour around 25–29 weeks of age was relatively “shy”, staying in shelter and avoiding open water. At around 37–41 weeks of age though, behaviour changed, with fish emerging from a hide more readily and exploring the environment. Interestingly, at 58 weeks of age fish were slower to initiate exploration, possibly indicating a return to “shyer” behaviour. All fish underwent thorough parasite examination, revealing no infections. We conclude that knowledge of the behaviour of hatchery-reared fish at different ages is useful for decisions around the timing of release that balance the needs of recreational fishers whilst managing the impact on freshwater ecosystem. Full article

In the world of finance, considerable attention is given to improving machine learning techniques to predict the future of stock markets. However, for obvious reasons, this turns out to be an unsolvable mission, most likely because the real world is not driven by algorithms but by human beings. In response to this, the present study has its focus on raw affective responses in actual asset managers during their decision making regarding controlled financial scenarios. Nineteen asset managers were invited and asked to make sell/buy decisions related to visual presentations of three different price developments of different assets. The three scenarios were “crash”, “stable” and “gain”. Parallel to their decision making, startle reflex modulation (SRM) was used to measure non-conscious affective responses without demanding any respective explicit responses (no conscious language processing involved). Interestingly, two further factors were introduced. First, all participants had to make their decisions once while being informed that 0% prior investments (low exposure) have been made into the presented assets, and once being informed that a large investment consisting of 25% of ones’ overall portfolio has been made prior to making the decision (high exposure). Second, the factor experience was included dividing all participants into two groups, one with low experience and the other with high experience. First, across both these extra factors, it was found that “crash” scenarios resulted in the most negative affective responses. The most positive affective responses were found for “gain” scenarios, while the “stable” condition was in between. Interestingly, the factor of prior investment (i.e., exposure) had an effect. Non-conscious affective responses during decision making related to the “stable” condition varied as a function of “exposure”. In the low exposure condition, affective responses to decision making during the “stable” scenario were most negative, even more negative than in “crash” scenarios. The factor experience also had an effect, but due to the small sample size, no significant interaction occurred. However, t-tests revealed the same significant effects in the experienced group as found in the 0% prior investment condition. To our knowledge, this is the first empirical investigation measuring non-conscious affective responses during decision making in the context of asset management. Thus, this study might form an interesting basis for new strategies to explore non-conscious human brain functions instead of inventing new algorithms to make asset management more successful. Full article