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Introduction: The effects of viral infections might be apolipoprotein E (apoE) isoform-dependent. In humans, there are three major apoE isoforms, E2, E3, and E4. E4 is associated with the enhanced entry of several viruses into the brain and their disease progression. A concern of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the development of post-acute COVID-19 syndrome, also known as long COVID. Genetic risk factors for developing long COVID were reported. Methods: In this study, we used virus-like particles (VLPs) that include expression of the SARS-CoV-2 nucleocapsid (N), membrane (M), and envelope (E) structural proteins together with S. In the current study, we used human E2, E3, and E4 targeted replacement mice to assess whether these VLPs affect body weight, behavioral and cognitive performance, and circadian body temperatures. Using VLPs allow working outside an ABSL-3 facility. Results: The effects of VLPs on some behavioral measures were apoE isoform-dependent, with the E2 mice being more affected than E3 or E4 mice. The overall decreased activity in the open field containing objects in week 2 indicate that VLPs can also reduce activity levels in an apoE isoform-independent fashion. Discussion: The results of the current study indicate that even in the absence of viral replication, detrimental effects of VLPs on behavioral measures and circadian body temperatures are seen. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy—the ARTiE Watch—to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures.We prospectively recruited patients admitted to the epilepsy monitoring units for diagnostic evaluation and long‐term video‐electroencephalographic monitoring at Mayo Clinic and Yale New Haven Hospital. Participants wore the ARTiE Watch, a smartwatch paired with custom smartphone software integrated with cloud infrastructure allowing for remote activation of standardized assessment on the participants' smartwatches. The assessment consisted of 18 command prompts that test behavioral responsiveness across motor, language, and memory domains. Upon visually identifying an electrographic seizure during EMU monitoring, the BrainRISE platform was used to deploy the ARTiE Watch behavioral testing sequence. Responsiveness scoring was conducted on smartwatch files.Eighteen of 56 participants had a total of 39 electrographic seizures assessed with the ARTiE Watch. The 18 subjects with ARTiE Watch‐tested seizures had a total of 67 baseline (interictal) ARTiE Watch tests collected for analysis. The analysis showed distinct ARTiE Watch behavioral responsiveness phenotypes: (1) decreased responsiveness across all ARTiE Watch commands during seizure (ictal–postictal) periods compared (to baseline (p < .0001), (2) decreased responsiveness in bilateral tonic–clonic seizures compared to baseline (p < .0001) and compared to focal seizures (p < .0001), and (3) decreased responsiveness during focal impaired awareness seizures compared to baseline (p < .0001) and compared to focal aware seizures (p < .001).ARTiE Watch behavioral testing deployed utilizing a mobile cloud‐based platform is feasible and can provide standardized, objective behavioral responsiveness assessments during seizures. [ABSTRACT FROM AUTHOR]

Background: Behavioral testing is widely used to measure individual differences in behavior and cognition among dogs and predict underlying psychological traits. However, the diverse applications, methodological variability, and lack of standardization in canine behavioral testing has posed challenges for researchers and practitioners seeking to use these tests. To address these complexities, this review sought to synthesize and describe behavioral testing methods by creating a framework that uses a “dog-centric” perspective to categorize the test stimuli used to elicit responses from dogs. Methods: A scoping review was conducted to identify scientific literature that has reported behavioral testing to assess psychological traits in dogs. Five online databases were systematically searched. Following this, an inductive content analysis was conducted to evaluate and summarize the behavioral testing methods in the literature. Results: A total of 392 publications met the selection criteria and were included in the analysis, collectively reporting 2,362 behavioral tests. These tests were individually evaluated and categorized. Our content analysis distinguished 29 subcategories of behavioral testing stimuli that have been used, grouped into three major categories: human-oriented stimuli; environmental stimuli; and motivator-oriented stimuli. Conclusion: Despite the methodological heterogeneity observed across behavioral testing methods, our study identified commonalities in many of the stimuli used in test protocols. The resulting framework provides a practical overview of published behavioral tests and their applications, which may assist researchers in selecting and designing appropriate tests for their purposes. [ABSTRACT FROM AUTHOR]

This document is a compilation of scientific articles that explore the historical treatment of rodents in scientific research and the growing recognition of their cognitive abilities and welfare. It emphasizes the importance of considering animal suffering and the need for animal-friendly methods in rodent behavioral testing. The articles discuss various approaches and technologies, such as mirror-based tests and automated monitoring systems, that prioritize animal welfare while providing valid results. The research presented in these articles sheds light on the complex behaviors and capabilities of rodents, highlighting their similarities to humans and the potential for further study in this field. [Extracted from the article]

This article discusses the historical treatment of rodents in scientific research and the need for improved methods that prioritize animal welfare. It highlights the growing recognition of rodents' cognitive abilities and challenges the notion that their welfare is less important due to their perceived inferiority. The article introduces a collection of contributions from researchers around the world that explore various approaches to animal-friendly behavioral testing for rodents. It discusses the importance of designing behavioral tests that consider the specific characteristics of different animal species and prioritize animal welfare. The text also highlights the contributions of various researchers in developing animal-friendly behavioral tests, including the use of mirror-based tests, infrared thermography, robotic animals, and automated home-cage monitoring systems. The article concludes by emphasizing the need for further development and exploration of new approaches in animal-friendly behavioral testing. This document is a list of references from various scientific articles related to animal behavior, specifically focusing on rodents such as mice and rats. The articles cover a range of topics including empathy, social behavior, cognitive abilities, and experimental methods for studying animal behavior. [Extracted from the article]

IntroductionThe effects of viral infections might be apolipoprotein E (apoE) isoform-dependent. In humans, there are three major apoE isoforms, E2, E3, and E4. E4 is associated with the enhanced entry of several viruses into the brain and their disease progression. A concern of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the development of post-acute COVID-19 syndrome, also known as long COVID. Genetic risk factors for developing long COVID were reported.MethodsIn this study, we used virus-like particles (VLPs) that include expression of the SARS-CoV-2 nucleocapsid (N), membrane (M), and envelope (E) structural proteins together with S. In the current study, we used human E2, E3, and E4 targeted replacement mice to assess whether these VLPs affect body weight, behavioral and cognitive performance, and circadian body temperatures. Using VLPs allow working outside an ABSL-3 facility.ResultsThe effects of VLPs on some behavioral measures were apoE isoform-dependent, with the E2 mice being more affected than E3 or E4 mice. The overall decreased activity in the open field containing objects in week 2 indicate that VLPs can also reduce activity levels in an apoE isoform-independent fashion.DiscussionThe results of the current study indicate that even in the absence of viral replication, detrimental effects of VLPs on behavioral measures and circadian body temperatures are seen.

BackgroundBehavioral testing is widely used to measure individual differences in behavior and cognition among dogs and predict underlying psychological traits. However, the diverse applications, methodological variability, and lack of standardization in canine behavioral testing has posed challenges for researchers and practitioners seeking to use these tests. To address these complexities, this review sought to synthesize and describe behavioral testing methods by creating a framework that uses a “dog-centric” perspective to categorize the test stimuli used to elicit responses from dogs.MethodsA scoping review was conducted to identify scientific literature that has reported behavioral testing to assess psychological traits in dogs. Five online databases were systematically searched. Following this, an inductive content analysis was conducted to evaluate and summarize the behavioral testing methods in the literature.ResultsA total of 392 publications met the selection criteria and were included in the analysis, collectively reporting 2,362 behavioral tests. These tests were individually evaluated and categorized. Our content analysis distinguished 29 subcategories of behavioral testing stimuli that have been used, grouped into three major categories: human-oriented stimuli; environmental stimuli; and motivator-oriented stimuli.ConclusionDespite the methodological heterogeneity observed across behavioral testing methods, our study identified commonalities in many of the stimuli used in test protocols. The resulting framework provides a practical overview of published behavioral tests and their applications, which may assist researchers in selecting and designing appropriate tests for their purposes.

The aim of the work was to study the influence of the researcher on the muscle strength assessment in animals in the experiment by comparing the results of the automated “inverted grid” test and its classical variant.Materials and methods. Male lines (Bla/J, n=20; FUS(1-359), n=20; Tau P301S+/+, n=20) and their background controls (C57BL/6J, n=20; CD1, n=20) were selected for the study. The dynamics of changes in the muscle deficit of the animals was evaluated in the automated and classical variant of the “inverted grid” test.Results. According to the results of the muscle strength assessment of mice with an edited genome of lines FUS(1-359)+/-, Tau P301S+/+, B6.ADysfprmd/GeneJ, using the “inverted grid” test in the classical variant and the automated one, it was found that statistically significant differences were not obtained in comparison with the results obtained by the classical variant of the test. The standard error of the mean increases by 23–39% in the classical test compared to the automated one. It was shown that the standard error of the mean in the classical variant of the test in Tau P301S+/+ mice was 6.24; 5.94; 5.88; 7.38 at 4 age points; in FUS(1-359)+/- mice, 4.49; 6.8; 6.98 and 4.1; B6.ADysfprmd/GeneJ mice, 7.66; 7.58; 8.3 and 7.92, respectively.Conclusion. Thus, the value of the standard error of the results study mean of the changes dynamics in the muscle strength when using the automated variant of the “inverted grid” test was reduced in comparison with the results of the classical variant of the test. The results of the study show that the automation of generally recognized behavioral tests is able to increase the accuracy of the obtained data reducing the influence of a human factor on the manipulation.

Behavioral testing constitutes the primary method to measure the emotional states of nonhuman animals in preclinical research. Emerging as the characteristic tool of the behaviorist school of psychology, behavioral testing of animals, particularly rodents, is employed to understand the complex cognitive and affective symptoms of neuropsychiatric disorders. Following the symptom-based diagnosis model of the DSM, rodent models and tests of depression and anxiety focus on behavioral patterns that resemble the superficial symptoms of these disorders. While these practices provided researchers with a platform to screen novel antidepressant and anxiolytic drug candidates, their construct validity—involving relevant underlying mechanisms—has been questioned. In this review, we present the laboratory procedures used to assess depressive- and anxiety-like behaviors in rats and mice. These include constructs that rely on stress-triggered responses, such as behavioral despair, and those that emerge with nonaversive training, such as cognitive bias. We describe the specific behavioral tests that are used to assess these constructs and discuss the criticisms on their theoretical background. We review specific concerns about the construct validity and translational relevance of individual behavioral tests, outline the limitations of the traditional, symptom-based interpretation, and introduce novel, ethologically relevant frameworks that emphasize simple behavioral patterns. Finally, we explore behavioral monitoring and morphological analysis methods that can be integrated into behavioral testing and discuss how they can enhance the construct validity of these tests. [ABSTRACT FROM AUTHOR]

Heterozygous carriers of the glucocerebrosidase 1 (GBA) L444P Gaucher mutation have an increased risk of developing Parkinson's disease (PD). The GBA mutations result in elevated alpha synuclein (aSyn) levels. Heterozygous mice carrying one allele with the L444P mutation knocked-into the mouse gene show increased aSyn levels and are more sensitive to motor deficits following exposure to the neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP than wild-type mice. Paraquat (PQ), a herbicide, increases PD risk in most studies. Its effects on the brain involve alterations in the gut microbiome. Exposure to dextran sulfate sodium (DSS), a mouse model of colitis, can be used to determine whether gut microbiome alterations are sufficient to induce PD-relevant phenotypes. We rederived the A53T-L444P and A53T mouse lines to assess whether PQ, PQ in combination with radiation exposure (IR), and DSS have differential effects in A53T and A53T-L444P mice and whether these effects are associated with alterations in the gut microbiome. PQ and PQ + IR have differential effects in A53T and A53T-L444P mice. In contrast, effects of DSS are only seen in A53T-L444P mice. Exposure and genotype modulate the relationship between the gut microbiome and behavioral performance. The gut microbiome may be an important mediator of how environmental exposures or genetic mutations yield behavioral and cognitive impacts. [ABSTRACT FROM AUTHOR]

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

Summary: Objective: Our primary goal was to measure the accuracy of fully automated absence seizure detection, using a wearable electroencephalographic (EEG) device. As a secondary goal, we also tested the feasibility of automated behavioral testing triggered by the automated detection. Methods: We conducted a phase 3 clinical trial (NCT04615442), with a prospective, multicenter, blinded study design. The input was the one‐channel EEG recorded with dry electrodes embedded into a wearable headband device connected to a smartphone. The seizure detection algorithm was developed using artificial intelligence (convolutional neural networks). During the study, the predefined algorithm, with predefined cutoff value, analyzed the EEG in real time. The gold standard was derived from expert evaluation of simultaneously recorded full‐array video‐EEGs. In addition, we evaluated the patients' responsiveness to the automated alarms on the smartphone, and we compared it with the behavioral changes observed in the clinical video‐EEGs. Results: We recorded 102 consecutive patients (57 female, median age = 10 years) on suspicion of absence seizures. We recorded 364 absence seizures in 39 patients. Device deficiency was 4.67%, with a total recording time of 309 h. Average sensitivity per patient was 78.83% (95% confidence interval [CI] = 69.56%–88.11%), and median sensitivity was 92.90% (interquartile range [IQR] = 66.7%–100%). The average false detection rate was.53/h (95% CI =.32–.74). Most patients (n = 66, 64.71%) did not have any false alarms. The median F1 score per patient was.823 (IQR =.57–1). For the total recording duration, F1 score was.74. We assessed the feasibility of automated behavioral testing in 36 seizures; it correctly documented nonresponsiveness in 30 absence seizures, and responsiveness in six electrographic seizures. Significance: Automated detection of absence seizures with a wearable device will improve seizure quantification and will promote assessment of patients in their home environment. Linking automated seizure detection to automated behavioral testing will provide valuable information from wearable devices. [ABSTRACT FROM AUTHOR]

Field studies of behavior provide insight into the expression of behavior in its natural ecological context and can serve as an important complement to behavioral studies conducted in the lab under controlled conditions. In addition to naturalistic observations, behavioral testing can be an important component of field studies of behavior. This mini review evaluates a sample of behavioral testing methods in field studies to identify ways in which behavioral testing can be animal-friendly and generate ethologically relevant data. Specific examples, primarily from studies of ground squirrels, are presented to illustrate ways in which principles of animal-friendly behavioral testing can be applied to and guide testing methods. Tests conducted with animals in their natural habitat and that elicit naturally occurring behavioral responses can minimize stress and disturbance for animals, as well as disruption of the larger ecosystem, and can have high ethological validity. When animals are trapped or handled as part of a study, behavioral testing can be incorporated into handling procedures to reduce overall disturbance. When behavior is evaluated in a testing arena, the arena can be designed to resemble natural conditions to increase the ethological relevance of the test. Efforts to minimize time spent in testing arenas can also reduce disturbance to animals. Adapting a behavioral test to a species or habitat conditions can facilitate reduced disruption to subjects and increased ethological relevance of the test. [ABSTRACT FROM AUTHOR]

Field studies of behavior provide insight into the expression of behavior in its natural ecological context and can serve as an important complement to behavioral studies conducted in the lab under controlled conditions. In addition to naturalistic observations, behavioral testing can be an important component of field studies of behavior. This mini review evaluates a sample of behavioral testing methods in field studies to identify ways in which behavioral testing can be animal-friendly and generate ethologically relevant data. Specific examples, primarily from studies of ground squirrels, are presented to illustrate ways in which principles of animal-friendly behavioral testing can be applied to and guide testing methods. Tests conducted with animals in their natural habitat and that elicit naturally occurring behavioral responses can minimize stress and disturbance for animals, as well as disruption of the larger ecosystem, and can have high ethological validity. When animals are trapped or handled as part of a study, behavioral testing can be incorporated into handling procedures to reduce overall disturbance. When behavior is evaluated in a testing arena, the arena can be designed to resemble natural conditions to increase the ethological relevance of the test. Efforts to minimize time spent in testing arenas can also reduce disturbance to animals. Adapting a behavioral test to a species or habitat conditions can facilitate reduced disruption to subjects and increased ethological relevance of the test.

Orofacial pain refers to pain occurring in the head and face, which is highly prevalent and represents a challenge to clinicians, but its underlying mechanisms are not fully understood, and more studies using animal models are urgently needed. Currently, there are different assessment methods for analyzing orofacial pain behaviors in animal models. In order to minimize the number of animals used and maximize animal welfare, selecting appropriate assessment methods can avoid repeated testing and improve the reliability and accuracy of research data. Here, we summarize different methods for assessing spontaneous pain, evoked pain, and relevant accompanying dysfunction, and discuss their advantages and disadvantages. While the behaviors of orofacial pain in rodents are not exactly equivalent to the symptoms displayed in patients with orofacial pain, animal models and pain behavioral assessments have advanced our understanding of the pathogenesis of such pain. [ABSTRACT FROM AUTHOR]

Intra-amniotic inflammation is a subclinical condition frequently caused by either microbial invasion of the amniotic cavity or sterile inflammatory stimuli, e.g., alarmins. An accumulating body of evidence supports a role for maternal immune activation in the genesis of fetal neuroinflammation and the occurrence of neurodevelopmental disorders such as cerebral palsy, schizophrenia, and autism. The objective of this study was to determine whether fetal exposure to mid-trimester intra-amniotic inflammation is associated with neurodevelopmental disorders in children eight to 12 years of age. This is a retrospective case-control study comprising 20 children with evidence of prenatal exposure to intra-amniotic inflammation in the mid-trimester and 20 controls matched for gestational age at amniocentesis and at delivery. Amniotic fluid samples were tested for concentrations of interleukin-6 and C-X-C motif chemokine ligand 10, for bacteria by culture and molecular microbiologic methods as well as by polymerase chain reaction for eight viruses. Neuropsychological testing of children, performed by two experienced psychologists, assessed cognitive and behavioral domains. Neuropsychological dysfunction was defined as the presence of an abnormal score (<2 standard deviations) on at least two cognitive tasks. Neuropsychological dysfunction was present in 45% (9/20) of children exposed to intra-amniotic inflammation but in only 10% (2/20) of those in the control group (p=0.03). The relative risk (RR) of neuropsychological dysfunction conferred by amniotic fluid inflammation remained significant after adjusting for gestational age at delivery [aRR=4.5 (1.07–16.7)]. Of the 11 children diagnosed with neuropsychological dysfunction, nine were delivered at term and eight of them had mothers with intra-amniotic inflammation. Children exposed to intra-amniotic inflammation were found to have abnormalities in neuropsychological tasks evaluating complex skills, e.g., auditory attention, executive functions, and social skills, whereas the domains of reasoning, language, and memory were not affected in the cases and controls. Asymptomatic sterile intra-amniotic inflammation in the mid-trimester of pregnancy, followed by a term birth, can still confer to the offspring a substantial risk for neurodevelopmental disorders in childhood. Early recognition and treatment of maternal immune activation in pregnancy may be a strategy for the prevention of subsequent neurodevelopmental disorders in offspring. [ABSTRACT FROM AUTHOR]

Development of novel approaches to behavioral test data analysis is of considerable importance for both fundamental research and experimental neuropharmacology. Antipsychotic agents used to treat positive and negative symptoms in schizophrenia are of particular interest. Although antipsychotics exert potent effects on animal behavior in simple behavioral tests, they can be difficult to distinguish from other CNS-depressing agents, such as sedatives. In this paper, we propose color coding of video sequences as a method for the analysis of behavioral pattern structure in rats, using the effects of haloperidol, a typical antipsychotic, in the Open field test as an example. The study was carried out on outbred albino male rats weighing 250–300 g. Three-min video sequences of rat behavior in the Open field test were processed using Python and the OpenCV library in the Google Colab 3 environment. Color coding allowed the present (t = 0), near-future (t = 0.33 s), and the more distant-future (t = 1.66 s) location of an animal in the Open field arena to be marked with different colors and overlaid within a single frame. Using the proposed 3-timepoint color coding method, we were able to detect specific effects of haloperidol on animal behavioral patterns, which are undetectable via conventional techniques of behavioral data analysis in the Open field test. This method proved effective for data analysis and processing, and the results were in accordance with other author's data obtained using computerized and conventional visualization techniques. [ABSTRACT FROM AUTHOR]

Chromone-containing allylmorpholines (CCAMs) are a novel class of compounds that have demonstrated acetyl- and butyryl-cholinesterase-inhibiting and N-methyl-D-aspartate (NMDA) receptor-blocking properties in vitro, but their in vivo pharmacological activity remains underexplored. In this work, we evaluated the psychotropic activity of five different CCAMs (1 (9a), 2 (9j), 3 (9l), 4 (33a), and 5 (33b)) using the novel tank test (NTT) and light/dark box (LDB) test in adult zebrafish. The CCAMs were screened in the NTT at a range of concentrations, and they were found to induce a dose-dependent sedative effect. Compound 4 (33a) was also evaluated using the LDB test, and it was found to have anxiolytic-like properties at low concentrations. To assess the potential contribution of the glutamate and cholinergic mechanisms in the effects of the CCAMs, we conducted experiments with pre-exposure to putative antagonists, NMDA and biperiden. Neither biperiden nor NMDA were able to diminish or cancel the effects of the CCAMs, countering the in vitro data obtained in previous studies. The apparent discrepancy could be related to the specifics of CCAM metabolism or to the interspecies differences between the putative target proteins, possibly due to the relatively low identity percentage of their sequences. Although further research in mammals is required in order to establish their pharmacological properties, novel CCAMs may represent an appealing group of psychoactive drug candidates. [ABSTRACT FROM AUTHOR]

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts. [ABSTRACT FROM AUTHOR]

The mid-dorsolateral prefrontal cortical region (areas 46 and 9/46) is critical for the monitoring of information in working memory both in the macaque monkey brain and the human brain. The presence of this cytoarchitectonic region in the New World marmoset brain was in debate, but recent anatomical evidence demonstrated a limited area 46. This finding raised the question of the extent to which the marmoset brain can support the cognitive control process of monitoring information within working memory. This cognitive control process was assessed in adult marmosets and was shown to be limited to the monitoring of only two items in contrast to macaque monkeys, who can monitor as many as five items in working memory. The results are consistent with the limited development of the relevant prefrontal region in the marmoset and contribute to understanding the evolution of higher cognitive control processes in the primate brain., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable to human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts.

The paper delivers a tribute to Professor Giambiasi by pointing out how the work and ideas stemming from the research performed under his umbrella in the 1980s on behavioral testing has been an inspiration for the research around DEVS formalism at the University of Corsica in the late 1990s and the beginning of the new century. The paper retraces how Giambiasi's heritage allowed researchers at the University of Corsica to go from behavioral and hierarchical testing to DEVS fault simulation. [ABSTRACT FROM AUTHOR]

Although plenty of evidences from preclinical studies have led to potential treatments for patients with spinal cord injury (SCI), the failure to translate promising preclinical findings into clinical advances has long puzzled researchers. Thus, a more reliable combination of anatomical assessment and behavioral testing is urgently needed to improve the translational worth of preclinical studies. To address this issue, the present study was designed to relate magnetic resonance imaging (MRI)-based anatomical assessment to behavioral outcome in a rat contusion model. Rats underwent contusion with three different heights to simulate various severities of SCI, and their locomotive functions were evaluated by the grid-walking test, Louisville swim scale (LSS), especially catwalk gait analysis system and basic testing, and Basso, Beattie, Bresnahan (BBB) score. The results showed that the lesion area (LA) is a better indicator for damage assessment compared with other parameters in sagittal T2-weighted MRI (T2WI). Although two samples are marked as outliers by the box plot analysis, LA correlated closely with all of the behavioral testing without ceiling effect and floor effect. Moreover, with a moderate severity of SCI in a contusion height of 25 mm, the smaller the LA of the spinal cord measured on sagittal T2WI the better the functional performance, the smaller the cavity region and glial scar, the more spared the myelin, the higher the volatility, and the thicker the bladder wall. We found that LA significantly related with behavior outcomes, which indicated that LA could be a proxy of damage assessment. The combination of sagittal T2WI and four types of behavioral testing can be used as a reliable scheme to evaluate the prognosis for preclinical studies of SCI. [ABSTRACT FROM AUTHOR]

Traditional methods of data analysis in animal behavior research are usually based on measuring behavior by manually coding a set of chosen behavioral parameters, which is naturally prone to human bias and error, and is also a tedious labor-intensive task. Machine learning techniques are increasingly applied to support researchers in this field, mostly in a supervised manner: for tracking animals, detecting land marks or recognizing actions. Unsupervised methods are increasingly used, but are under-explored in the context of behavior studies and applied contexts such as behavioral testing of dogs. This study explores the potential of unsupervised approaches such as clustering for the automated discovery of patterns in data which have potential behavioral meaning. We aim to demonstrate that such patterns can be useful at exploratory stages of data analysis before forming specific hypotheses. To this end, we propose a concrete method for grouping video trials of behavioral testing of animal individuals into clusters using a set of potentially relevant features. Using an example of protocol for testing in a “Stranger Test”, we compare the discovered clusters against the C-BARQ owner-based questionnaire, which is commonly used for dog behavioral trait assessment, showing that our method separated well between dogs with higher C-BARQ scores for stranger fear, and those with lower scores. This demonstrates potential use of such clustering approach for exploration prior to hypothesis forming and testing in behavioral research.

Although plenty of evidences from preclinical studies have led to potential treatments for patients with spinal cord injury (SCI), the failure to translate promising preclinical findings into clinical advances has long puzzled researchers. Thus, a more reliable combination of anatomical assessment and behavioral testing is urgently needed to improve the translational worth of preclinical studies. To address this issue, the present study was designed to relate magnetic resonance imaging (MRI)-based anatomical assessment to behavioral outcome in a rat contusion model. Rats underwent contusion with three different heights to simulate various severities of SCI, and their locomotive functions were evaluated by the grid-walking test, Louisville swim scale (LSS), especially catwalk gait analysis system and basic testing, and Basso, Beattie, Bresnahan (BBB) score. The results showed that the lesion area (LA) is a better indicator for damage assessment compared with other parameters in sagittal T2-weighted MRI (T2WI). Although two samples are marked as outliers by the box plot analysis, LA correlated closely with all of the behavioral testing without ceiling effect and floor effect. Moreover, with a moderate severity of SCI in a contusion height of 25 mm, the smaller the LA of the spinal cord measured on sagittal T2WI the better the functional performance, the smaller the cavity region and glial scar, the more spared the myelin, the higher the volatility, and the thicker the bladder wall. We found that LA significantly related with behavior outcomes, which indicated that LA could be a proxy of damage assessment. The combination of sagittal T2WI and four types of behavioral testing can be used as a reliable scheme to evaluate the prognosis for preclinical studies of SCI.

Adverse effects of drugs on the human nervous system are rarely possible to anticipate based on preclinical neurotoxicity data, thus propagating the centuries long single most important obstacle to drug discovery and development for disorders of the nervous system. An emerging body of evidence indicates that in vivo electrophysiology using chronically implanted high-density electrodes (ciHDE) in freely moving animals is a rigorous method with enhanced potential for use in translational research. In particular, the structure and function of the hippocampal trisynaptic circuit (HTC) is conserved from rodents to primates, including Homo sapiens, suggesting that the effects of therapeutic agents and other potential neurologically active agents, whether beneficial or adverse, are likely to translate across species when interrogated using a conserved neural circuitry platform. This review explores science advances in the rapidly moving field of in vivo ciHDE in animal models of learning and memory. For this reason we focus on the HTC, where substantial research has investigated neural circuitry level responses and specific behaviors that reflect memory permitting a test of the ground truth validity of the findings. Examples of changes in neural network activity induced by endogenous neurotoxicants associated with neurodegenerative diseases, as well as exogenous therapeutics, drugs, and neurotoxicants are presented. Several illustrative examples of relevant findings that involve longer range neural circuitry outside of the HTC are discussed. Lastly, the limitations of in vivo ciHDE as applied to preclinical neurotoxicology are discussed with a view toward leveraging circuitry level actions to enhance our ability to project the specificity of in vitro target engagement with the desired psychopharmacological or neurological outcome. At the same time, the goal of reducing or eliminating significant neurotoxic adverse events in human is the desired endpoint. We believe that this approach will lead to enhanced discovery of high value neuroactive therapeutics that target neural circuitry domains as their primary mechanism of action, thus enhancing their ultimate contribution toward discovery of precision therapeutics.

Preclinical animal models are indispensable tools for translational research for which behavioral characterization and phenotyping are essential to testing hypotheses and for evaluating the potential of novel therapeutic agents to treat diseases. The methods employed for comprehensive behavioral phenotyping and pharmacological experiments are complex and should be conducted exclusively by trained technicians with demonstrated proficiency. The ultimate goal is to identify disease-relevant and translational behavioral endpoints that are robust, reliable, and reproducible, and that can be employed to evaluate potential of novel therapeutic agents to treat disease. The intent of the present article is to provide a pragmatic outline for establishing and optimizing behavioral assays and phenotyping batteries, ensuring that the assays and the data are reliable such that they can be reproduced within and across technicians and laboratories and, more importantly, that the data is translatable to the clinic. © 2016 by John Wiley & Sons, Inc.

The gut microbiome and the gut brain axis are potential determinants of Alzheimer's disease (AD) etiology or severity and gut microbiota might coordinate with the gut-brain axis to regulate behavioral phenotypes in AD mouse models. Using 6-month-old human amyloid precursor protein (hAPP) knock-in (KI) mice, which contain the Swedish and Iberian mutations [APP NL-F (App NL–F)] or the Arctic mutation as third mutation [APP NL-G-F (App NL–G–F)], behavioral and cognitive performance is associated with the gut microbiome and APP genotype modulates this association. In this study, we determined the feasibility of behavioral testing of mice in a biosafety cabinet and whether stool from 6-month-old App NL–G–F mice or App NL–G–F crossed with human apoE4 targeted replacement mice is sufficient to induce behavioral phenotypes in 4-5 month-old germ-free C57BL/6J mice 4 weeks following inoculation. We also compared the behavioral phenotypes of the recipient mice with that of the donor mice. Finally, we assessed cortical Aβ levels and analyzed the gut microbiome in the recipient mice. These results show that it is feasible to behaviorally test germ-free mice inside a biosafety cabinet. However, the host genotype was critical in modulating the pattern of induced behavioral phenotypes as compared to those seen in the genotype- and sex-match donor mice. Male mice that received stool from App NL–G–F and App NL–G–F/E4 donor genotypes tended to have lower body weight as compared to wild type, an effect not observed among donor mice. Additionally, App NL–G–F/E4 recipient males, but not females, showed impaired object recognition. Insoluble Aβ40 levels were detected in App NL–G–F and App NL–G–F/E4 recipient mice. Recipients of App NL–G–F, but not App NL–G–F/E4, donor mice carried cortical insoluble Aβ40 levels that positively correlated with activity levels on the first and second day of open field testing. For recipient mice, the interaction between donor genotype and several behavioral scores predicted gut microbiome alpha-diversity. Similarly, two behavioral performance scores predicted microbiome composition in recipient mice, but this association was dependent on the donor genotype. These data suggest that genotypes of the donor and recipient might need to be considered for developing novel therapeutic strategies targeting the gut microbiome in AD and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Livestock guarding dogs (LGDs) are used all over the world to help in carnivore conservation by mitigating human-wildlife conflict. In Namibia, LGDs are used in cheetah conservation to prevent depredation of stock and reduce retaliatory killings. However, behavioral problems in the dogs, such as chasing wildlife and harassing livestock, exist leading to poor dog performance and farmer dissatisfaction. In most other types of working dogs, behavior tests for suitability are reported and/or validated within the scientific literature. To date this has not been done for LGDs. In this paper, we design a composite behavioral test and a questionnaire to rate the dogs' effectiveness as an LGD. This test was used on 14 LGDs, 7 of which were operational and 7 of which were being used as breeding stock. In total, 16 behavioral variables were measured. A Principal Components Analysis reduced these to 5 underlying personality traits: "Playfulness," "Trainability," "Independence," "Sociability with people" and "Reactivity." When 14 dogs were tested 3 times, 20 days apart, the traits "Playfulness," "Trainability" and "Independence" were found to be consistent. "Trainability" was negatively correlated to dog age. Dogs with a higher "Trainability" and lower "Reactivity" showed a tendency to be rated as more effective by their herdsman. Dogs scoring higher for "Playfulness" were more likely to be reported to harass stock, and dogs that chased a moving object under experimental conditions were generally rated higher for tendency to chase predator wildlife when working. This study suggests that there are personality attributes which can be measured and are consistent across time in LGDs. Several of these are linked to better performance in trained dogs. Whether these are predictive of later performance in untrained dogs, is yet to be ascertained. [ABSTRACT FROM AUTHOR]

Research background. Depression has become a global threat to human health. In order to solve it, researchers have conducted multi-faceted studies including diet. Many food-derived bioactive substances have shown antidepressant effects. However, there are few studies on the design of industrialized food with antidepressant effect. This study aims to evaluate the antidepressant effect of afunctional beverage made from several ingredients with potential antidepressant function and investigate its antidepressant mechanisms. Experimental approach. The beverage consists of peppermint oil, active peptides derived from bovine milk casein and Acanthopanax senticosus extract (ASE) whose active ingredient is eleutheroside. Different amounts of ASE were evaluated to determine the optimal concentration of eleutheroside in this functional beverage to deliver the best antidepressant effect through extensive behavioral testing, including preliminary acute stress experiments and further chronic unpredictable mild stress test. Results and conclusions. The results demonstrated that the beverage with 15 mg/kg of eleutheroside could significantly reduce the mice’s immobility time of tail suspension test and forced swimming test, recover mice’s sucrose preference and behavior changes in the open field test, improve the contents of dopamine, norepinephrine, 5-hydroxytryptamine and the activity of superoxide dismutase and reduce the content of malondialdehyde in mice’s brains, which indicated that the improvement of monoamine neurotransmitter systems and antioxidation was one potential mechanism of antidepressant action. Novelty and scientific contribution. This study provides a design of antidepressant functional beverage and an efficient way for the prevention and treatment of depression.

The gut microbiome and the gut brain axis are potential determinants of Alzheimer’s disease (AD) etiology or severity and gut microbiota might coordinate with the gut-brain axis to regulate behavioral phenotypes in AD mouse models. Using 6-month-old human amyloid precursor protein (hAPP) knock-in (KI) mice, which contain the Swedish and Iberian mutations [APP NL-F (AppNL–F)] or the Arctic mutation as third mutation [APP NL-G-F (AppNL–G–F)], behavioral and cognitive performance is associated with the gut microbiome and APP genotype modulates this association. In this study, we determined the feasibility of behavioral testing of mice in a biosafety cabinet and whether stool from 6-month-old AppNL–G–F mice or AppNL–G–F crossed with human apoE4 targeted replacement mice is sufficient to induce behavioral phenotypes in 4-5 month-old germ-free C57BL/6J mice 4 weeks following inoculation. We also compared the behavioral phenotypes of the recipient mice with that of the donor mice. Finally, we assessed cortical Aβ levels and analyzed the gut microbiome in the recipient mice. These results show that it is feasible to behaviorally test germ-free mice inside a biosafety cabinet. However, the host genotype was critical in modulating the pattern of induced behavioral phenotypes as compared to those seen in the genotype- and sex-match donor mice. Male mice that received stool from AppNL–G–F and AppNL–G–F/E4 donor genotypes tended to have lower body weight as compared to wild type, an effect not observed among donor mice. Additionally, AppNL–G–F/E4 recipient males, but not females, showed impaired object recognition. Insoluble Aβ40 levels were detected in AppNL–G–F and AppNL–G–F/E4 recipient mice. Recipients of AppNL–G–F, but not AppNL–G–F/E4, donor mice carried cortical insoluble Aβ40 levels that positively correlated with activity levels on the first and second day of open field testing. For recipient mice, the interaction between donor genotype and several behavioral scores predicted gut microbiome alpha-diversity. Similarly, two behavioral performance scores predicted microbiome composition in recipient mice, but this association was dependent on the donor genotype. These data suggest that genotypes of the donor and recipient might need to be considered for developing novel therapeutic strategies targeting the gut microbiome in AD and other neurodegenerative disorders.

Orofacial pain refers to pain occurring in the head and face, which is highly prevalent and represents a challenge to clinicians, but its underlying mechanisms are not fully understood, and more studies using animal models are urgently needed. Currently, there are different assessment methods for analyzing orofacial pain behaviors in animal models. In order to minimize the number of animals used and maximize animal welfare, selecting appropriate assessment methods can avoid repeated testing and improve the reliability and accuracy of research data. Here, we summarize different methods for assessing spontaneous pain, evoked pain, and relevant accompanying dysfunction, and discuss their advantages and disadvantages. While the behaviors of orofacial pain in rodents are not exactly equivalent to the symptoms displayed in patients with orofacial pain, animal models and pain behavioral assessments have advanced our understanding of the pathogenesis of such pain.

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15mg/kg, ip) and then were rescued from lethality by administration of diazepam (5mg/kg, ip) approximately 20min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72s. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1week, 1month and 2months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2months post-TETS intoxication. The general absence of long-term behavioral deficits in TETS-intoxicated mice on these six assays suggests that the neurobehavioral consequences of TETS exposure described in human survivors of acute TETS intoxication are likely due to sustained seizure activity, rather than a direct effect of the chemical itself. Future research efforts are directed toward developing an animal model that better recapitulates the SE and seizure duration reported in humans acutely intoxicated with TETS.

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated. • A new method: Modified Multiple Platform Method combined with alternate-day fasting. • Modeling method has successfully constructed animal model of central fatigue. • Our rat model mimics human emotional, cognitive, and physical fatigue. • Hippocampus and muscle tissues show damage and mitochondrial changes. • Mitochondrial dysfunction and oxidative stress in hippocampus and muscle tissues. [ABSTRACT FROM AUTHOR]

Some species of Codonopsis (local name in Shanxi: Ludang) have long demonstrated high medicinal and economic value. Radix Codonopsis, the dried root of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. modesta (Nannf.) L.D.Shen (C. pilosula var. modesta), or Codonopsis pilosula subsp. tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), was recorded as a traditional Chinese medicine back in the Qing Dynasty in Ben Cao Cong Xin. Radix Codonopsis, a valuable medicinal herb certified by the Chinese National Geographic Indication, is known for invigorating the spleen, nourishing the lungs, promoting blood circulation, and generating fluid properties. Given that chronic cerebral ischemia (CCI) is often associated with the symptoms of qi and blood deficiencies and fluid depletion, we explored the potential of Codonopsis decoction in the treatment of CCI. We investigated the effects of Codonopsis decoction on cerebral blood flow (CBF) and cognitive function in rats with bilateral carotid artery occlusion after surgery; explored whether Codonopsis decoction alleviates pathological injuries in brain tissue of rats after 2-VO surgery; and assessed the impact of Codonopsis decoction on the expression of chemokines, hypoxia-inducible factors, and inflammatory mediators in rats after 2-VO surgery. We used a 2-VO rat model to simulate CCI. We used a laser speckle imaging (LSI) system to observe changes in CBF before and after surgery. The goal was to examine variations in CBF at different time points after 2-VO surgery. For 4 weeks, the rats were orally administered Codonopsis decoction at doses of 2.7, 5.4, and 10.8 g/kg/day, or Ginaton at a dose of 43.2 mg/kg/day. To assess the effect of Codonopsis on cerebral hypoperfusion symptoms in rats, we conducted the Morris water maze (MWM), Barnes maze (BM), and forelimb grip strength tests. Additionally, pathological experiments including hematoxylin and eosin, Nissl, and Luxol fast blue staining were conducted. Furthermore, we used western blotting to detect changes in the levels of proteins such as the chemotactic factor CKLF1 and hypoxia-inducible actor 1-alpha (HIF-1α). One week after 2-VO surgery, cerebral arterial blood supply in the rats rapidly reduced to approximately 43.39% ± 3.53% of the preoperative level. Cerebral cortex perfusion reached its nadir within 24 h of surgery, gradually recovering and stabilizing by the fourth week after surgery. An integration of the results from the BM, MWM, and grip strength tests, which assessed cognitive function and forelimb strength in rats after 2-VO surgery, unequivocally revealed that Codonopsis treatment significantly reduced the latency period and increased the number of platform crossings in the MWM test. Ginaton exhibited a comparable effect. Moreover, both Codonopsis and Ginaton decreased the number of errors and the time required to locate the target hole in the BM test. Histopathological staining revealed that Codonopsis and Ginaton could ameliorate pathological damage in rats after CCI and reduce the release of factors such as CKLF1 and HIF-1α. Codonopsis decoction exerted its protective effects on CCI rats possibly by modulating the levels of chemokines, hypoxia-inducible factors, and neuroinflammatory mediators. [Display omitted] • Codonopsis decoction enhances CBF and mitigates cognitive dysfunction in rats after CCI. • The functional aspect of this decoction in nourishing the center and benefiting qi is manifested in its ability to reduce the hypoxia-induced release of chemotactic factors. • This decoction can transform the phenotype of microglial cells from the pro-inflammatory to the anti-inflammatory type. [ABSTRACT FROM AUTHOR]

Abstract Background Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-d-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. The aim of this study was to assess the behavioral effects of acute inhalation of subanesthetic concentrations of Xe and to study the outcomes of Xe exposure in valproic acid (VPA)-induced rodent model of autism. Methods We have conducted two series of experiments with a battery of behavioral tests aimed to evaluate locomotion, anxiety- and depression-like behavior, and social behavior in healthy, VPA-treated and Xe-exposed young rats. Results We have shown that in healthy animals Xe exposure resulted in acute and delayed decrease of exploratory motivation, partial decrease in risk-taking and depressive-like behavior as well as improved sensorimotor integration during the negative geotaxis test. Acute inhalations of Xe in VPA-exposed animals led to improvement in social behavior, decrease in exploratory motivation, and normalization of behavior in forced-swim test. Conclusion Behavioral modulatory effects of Xe are probably related to its generalized action on excitatory/inhibitory balance within the CNS. Our data suggest that subanesthetic short-term exposures to Xe have beneficial effect on several behavioral modalities and deserves further investigation.

The disposal of untreated sanitary sewage in the soil has several consequences for human health and leads to environmental risks; thus, it is necessary investigating, monitoring and remediating the affected sites. The aims of the current study are to evaluate ecotoxicological effects on Eisenia andrei earthworms exposed to soil subjected to sources of sanitary sewage discharge and to investigate whether prevention values established by the Brazilian legislation for soil quality, associated with the incidence of chemical substances in it, are satisfactory enough to assure the necessary quality for different organisms. Earthworms’ behavior, reproduction, acetylcholinesterase activity, catalase, superoxide dismutase and malondialdehyde levels were evaluated. The reproduction and behavior of earthworms exposed to sanitary sewage were adversely affected. Increased superoxide dismutase and catalase activity acted as antioxidant defense mechanism. Significantly increased lipid peroxidation levels and acetylcholinesterase activity inhibition have indicated lipid peroxidation in cell membrane and neurotransmission changes, respectively. Results have confirmed that sanitary sewage induced oxidative stress in earthworms. In addition, based on biochemical data analysis, the integrated biomarker response (IBR) has evidenced different toxicity levels in earthworms between the investigated points. Finally, results have indicated that effluents released into the soil, without proper treatment, lead to contaminant accumulation due to soil saturation and it can hinder different processes and biological development taking place in the soil. In addition, the current study has shown that physical-chemical analyses alone are not enough to assess soil quality, since it is also requires adopting an ecotoxicological approach. Brazilian legislation focused on soil quality must be revised and new guiding values must be proposed.

BackgroundTo produce and understand words, humans access the mental lexicon. From a functional perspective, the long-term memory component of the mental lexicon is comprised of three levels: the concept level, the lemma level, and the phonological level. At each level, different kinds of word information are stored. Semantic as well as phonological cues can help to facilitate word access during a naming task, especially when neural dysfunctions are present. The processing corresponding to word access occurs in specific parts of working memory. Neural models for simulating speech processing help to uncover the complex relationships that exist between neural dysfunctions and corresponding behavioral patterns.MethodsThe Neural Engineering Framework (NEF) and the Semantic Pointer Architecture (SPA) are used to develop a quantitative neural model of the mental lexicon and its access during speech processing. By simulating a picture-naming task (WWT 6-10), the influence of cues is investigated by introducing neural dysfunctions within the neural model at different levels of the mental lexicon.ResultsFirst, the neural model is able to simulate the test behavior for normal children that exhibit no lexical dysfunction. Second, the model shows worse results in test performance as larger degrees of dysfunction are introduced. Third, if the severity of dysfunction is not too high, phonological and semantic cues are observed to lead to an increase in the number of correctly named words. Phonological cues are observed to be more effective than semantic cues.ConclusionOur simulation results are in line with human experimental data. Specifically, phonological cues seem not only to activate phonologically similar items within the phonological level. Moreover, phonological cues support higher-level processing during access of the mental lexicon. Thus, the neural model introduced in this paper offers a promising approach to modeling the mental lexicon, and to incorporating the mental lexicon into a complex model of language processing.

Depression caused by genetic and environmental factors is acomplicated disease. Here, it is demonstrated that glycogen synthase kinase-3$\beta$ is highly expressed and phosphorylated in the brain of a chronic stress mouse. Inhibition of glycogen synthase kinase-3$\beta$ leads to decreased depression-like symptoms which manifest in open-field test, tail-suspension test, forced-swim test, and a novelty suppressed feeding test. It was also found that $\beta$-catenin is attenuated, and its target genes Cyclin D1 and c-Myc are down-regulated. Glycogen synthase kinase-3$\beta$ was also found to inhibit Erk-Creb-BDNF signaling. These results show that glycogen synthase kinase-3$\beta$ may promote the progression of depression. Therefore, targeting glycogen synthase kinase-3$\beta$ may be an effective therapeutic strategy.

Ficus religiosa has been extensively used in traditional medicine for the treatment of gonorrhea, diarrhea, dysentery, leucorrhea, menorrhagia, vaginal and other urogenital disorders, haemorrhoids and ulcers, but limited information is available regarding their effect on behavior. The present study was designed to demonstrate the effect of F. religiosa leaf extract on the selected behavioral aspect of albino mice. Four weeks old albino mice of both genders were orally treated with 50 mg ml−1 solvent kg−1 body weight of F. religiosa leaf extract for seven days while the control animals were treated with saline (0.9% NaCl) solution. A battery of neurological tests (rota rod, open field, light dark box, elevated plus maze and novel object recognition) was conducted in all subjects. Female mice treated with F. religiosa leaf extract had significantly reduced rota rod performance in comparison with the control. Male mice treated with leaf extract had significantly reduced transition frequency during light dark box test while during elevated plus maze test, male mice remained mobile for less time and had reduced rotations than their control group. Male mice treated with leaf extract had significantly reduced line crossing and failed to recognize the old object during the second trial of novel object recognition test. Our results indicated that oral supplementation of F. religiosa leaf extract for seven days had significantly reduced the exploratory behavior and object recognition capacity of male mice and neuromuscular coordination of females, indicating gender specific effects of the applied ethanolic leaf extract. [ABSTRACT FROM AUTHOR]

Background: Attention impairment is an under-investigated feature and diagnostic criterion of Major Depressive Disorder (MDD) that is associated with poorer outcomes. Despite increasing knowledge regarding mechanisms of attention in healthy adults, we lack a detailed characterization of attention impairments and their neural signatures in MDD. Methods: Here, we focus on selective attention and advance a deep multi-modal characterization of these impairments in MDD, using data acquired from n = 1008 patients and n = 336 age- and sex-matched healthy controls. Selective attention impairments were operationalized and anchored in a behavioral performance measure, assessed within a battery of cognitive tests. We sought to establish the accompanying neural signature using independent measures of functional magnetic resonance imaging (15% of the sample) and electroencephalographic recordings of oscillatory neural activity. Results: Greater impairment on the behavioral measure of selective attention was associated with intrinsic hypo-connectivity of the fronto-parietal attention network. Not only was this relationship specific to the fronto-parietal network unlike other large-scale networks; this hypo-connectivity was also specific to selective attention performance unlike other measures of cognition. Selective attention impairment was also associated with lower posterior alpha (8–13 Hz) power at rest and was related to more severe negative bias (frequent misidentifications of neutral faces as sad and lingering attention on sad faces), relevant to clinical features of negative attributions and brooding. Selective attention impairments were independent of overall depression severity and of worrying or sleep problems. Conclusions: These results provide a foundation for the clinical translational development of objective markers and targeted therapeutics for attention impairment in MDD. [ABSTRACT FROM AUTHOR]

Background: To produce and understand words, humans access the mental lexicon. From a functional perspective, the long-term memory component of the mental lexicon is comprised of three levels: the concept level, the lemma level, and the phonological level. At each level, different kinds of word information are stored. Semantic as well as phonological cues can help to facilitate word access during a naming task, especially when neural dysfunctions are present. The processing corresponding to word access occurs in specific parts of working memory. Neural models for simulating speech processing help to uncover the complex relationships that exist between neural dysfunctions and corresponding behavioral patterns. Methods: The Neural Engineering Framework (NEF) and the Semantic Pointer Architecture (SPA) are used to develop a quantitative neural model of the mental lexicon and its access during speech processing. By simulating a picture-naming task (WWT 6-10), the influence of cues is investigated by introducing neural dysfunctions within the neural model at different levels of the mental lexicon. Results: First, the neural model is able to simulate the test behavior for normal children that exhibit no lexical dysfunction. Second, the model shows worse results in test performance as larger degrees of dysfunction are introduced. Third, if the severity of dysfunction is not too high, phonological and semantic cues are observed to lead to an increase in the number of correctly named words. Phonological cues are observed to be more effective than semantic cues. Conclusion: Our simulation results are in line with human experimental data. Specifically, phonological cues seem not only to activate phonologically similar items within the phonological level. Moreover, phonological cues support higher-level processing during access of the mental lexicon. Thus, the neural model introduced in this paper offers a promising approach to modeling the mental lexicon, and to incorporating the mental lexicon into a complex model of language processing. [ABSTRACT FROM AUTHOR]