Standard Behavioral Tests Research Articles

Inhalation of H2/O2 (66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage

Diabetes mellitus complicated with depression (DD) is a prevalent psychosomatic disorder. It is characterized by severe cognitive impairment, and associated with high rates of disability and mortality. Although conventional treatment options are available, the efficacy of these regimens in managing DD remains limited. Molecular hydrogen (H2), a selective hydroxyl radical scavenger, has shown therapeutic potential in the treatment of various systemic diseases. This study aims to investigate the therapeutic effects of H2 on DD. A DD mouse model was established through intraperitoneal injection of streptozotocin (STZ, 150 mg/kg) and lipopolysaccharide (LPS, 0.5 mg/kg). Following the induction of DD, the mice were treated with H2/O2 (66.7 %/33.3 %)inhalation for 7 days. Behavioral assessments were conducted by standard behavioral tests, and the levels of inflammatory cytokines in peripheral blood serum and hippocampal tissue were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, magnetic resonance imaging (MRI) scans and immunofluorescence staining of the hippocampus were performed to evaluate hippocampal structural integrity. The results demonstrated that inhalation of H2/O2 (66.7 %/33.3 %) significantly ameliorated depressive behaviors and symptoms in DD mice, reversed hippocampal volume reduction, decreased inflammatory cytokine levels in peripheral blood serum and hippocampal tissue, and inhibited the activation of A1 astrocytes in the hippocampus. Our study suggests that H2/O2 (66.7 %/33.3 %) inhalation therapy may offer a promising treatment strategy for DD and its associated symptoms.

Audiogram Estimation Performance Using Auditory Evoked Potentials and Gaussian Processes.

Auditory evoked potentials (AEPs) play an important role in evaluating hearing in infants and others who are unable to participate reliably in behavioral testing. Discriminating the AEP from the much larger background activity, however, can be challenging and time-consuming, especially when several AEP measurements are needed, as is the case for audiogram estimation. This task is usually entrusted to clinicians, who visually inspect the AEP waveforms to determine if a response is present or absent. The drawback is that this introduces a subjective element to the test, compromising quality control of the examination. Various objective methods have therefore been developed to aid clinicians with response detection. In recent work, the authors introduced Gaussian processes (GPs) with active learning for hearing threshold estimation using auditory brainstem responses (ABRs). The GP is attractive for this task, as it can exploit the correlation structure underlying AEP waveforms across different stimulus levels and frequencies, which is often overlooked by conventional detection methods. GPs with active learning previously proved effective for ABR hearing threshold estimation in simulations, but have not yet been evaluated for audiogram estimation in subject data. The present work evaluates GPs with active learning for ABR audiogram estimation in a sample of normal-hearing and hearing-impaired adults. This involves introducing an additional dimension to the GP (i.e., stimulus frequency) along with real-time implementations and active learning rules for automated stimulus selection. The GP's accuracy was evaluated using the "hearing threshold estimation error," defined as the difference between the GP-estimated hearing threshold and the behavioral hearing threshold to the same stimuli. Test time was evaluated using the number of preprocessed and artifact-free epochs (i.e., the sample size) required for locating hearing threshold at each frequency. Comparisons were drawn with visual inspection by examiners who followed strict guidelines provided by the British Society of Audiology. Twenty-two normal hearing and nine hearing-impaired adults were tested (one ear per subject). For each subject, the audiogram was estimated three times: once using the GP approach, once using visual inspection by examiners, and once using a standard behavioral hearing test. The GP's median estimation error was approximately 0 dB hearing level (dB HL), demonstrating an unbiased test performance relative to the behavioral hearing thresholds. The GP additionally reduced test time by approximately 50% relative to the examiners. The hearing thresholds estimated by the examiners were 5 to 15 dB HL higher than the behavioral thresholds, which was consistent with the literature. Further testing is still needed to determine the extent to which these results generalize to the clinic. GPs with active learning enable automatic, real-time ABR audiogram estimation with relatively low test time and high accuracy. The GP could be used to automate ABR audiogram estimation or to guide clinicians with this task, who may choose to override the GP's decisions if deemed necessary. Results suggest that GPs hold potential for next-generation ABR hearing threshold and audiogram-seeking devices.

Advancing Alzheimer's Research With Zebrafish Models: Current Insights, Addressing Challenges, and Charting Future Courses.

Alzheimer's disease (AD) is a neurological condition that progressively impairs cognitive function and results in memory loss.Despite substantial research efforts, little is known about the specific processes driving AD, and there are few proven therapies. Because of their physiological and genetic resemblance to humans, zebrafish (Danio rerio) have become an important model organism for furthering research on AD.This abstract discusses the difficulties faced, looks at the insights currently garnered from zebrafish models, and suggests future research options. AD knowledge has greatly benefited from the use of zebrafish models. Transgenic zebrafish that express human AD-associated genes, such as tau and amyloid precursor protein (APP), display tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques, two of the disease's main clinical characteristics. These models have clarified the roles of oxidative stress, inflammation, and calcium homeostasis in the course of AD and allowed for the purpose of high-throughput screening of potential therapeutic agents.Understanding the growth and deterioration of neurons has been greatly aided by real-time zebrafish imaging. Fully using zebrafish models in AD research requires addressing a number of issues. The dissimilarities in zebrafish anatomy and physiology from humans, the difficulty of developing models that replicate progressive and late-onset AD (LOAD), and the requirement for standardized procedures to evaluate alterations in zebrafish cognition and behavior are a few issues.Furthermore, variations in the genetic makeup of zebrafish strains might affect the results of experiments. Future directions include developing standardized behavioral assays and cognitive tests, working together to create extensive databases of zebrafish genetic and phenotypic data, and using genetic engineering techniques like CRISPR/Cas9 to create more complex zebrafish models. Combining zebrafish models with other model species helps expedite the conversion of research results into therapeutic applications and offers a more thorough knowledge of AD.To sum up, zebrafish models have made a substantial contribution to Alzheimer's research by offering insightful information on the causes of the illness and possible therapies. By tackling present issues and formulating a planned future path, we can improve the use of zebrafish to decipher the mysteries of Alzheimer's and help create successful treatments.

Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models

BackgroundCurrent phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a “behavioral fingerprint” that takes environmental and sex influences under consideration. MethodsTo this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays—the Live Mouse Tracker and Motion Sequencing—on male and female Shank2, Tsc1, and Purkinje cell–specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. ResultsMultiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. ConclusionsTogether, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models.

Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.

Overexpression of the agouti-signaling protein (asip1), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] (asip1-Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1-Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1-Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1-Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1-Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Efficacy assessment of novel methanimine derivatives in chronic constriction injury-induced neuropathic model: An in-vivo, ex-vivo and In-Silico approach

The multicomponent etiology, complex clinical implications, dose-based side effect and degree of pain mitigation associated with the current pharmacological therapy is incapable in complete resolution of chronic neuropathic pain patients which necessitates the perpetual requirement of novel medication therapy. Therefore, this study explored the ameliorative aptitude of two novel methanimine imitative like (E)-N-(4-nitrobenzylidene)-4‑chloro-2-iodobenzamine (KB 09) and (E)-N-(4-methylbenzylidene)-4‑chloro-2-iodobenzamine (KB 10) in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rat model. Standard behavioral tests like dynamic and static allodynia, cold, thermal and mechanical hyperalgesia along with rotarod activity were performed at various experimental days like 0, 3, 7, 14 and 21. Enzyme linked immunosorbent assay (ELISA) on spinal tissue and antioxidant assays on sciatic nerve were executed accompanied by molecular docking and simulation studies. Prolonged ligation of sciatic nerve expressively induced hyperalgesia as well as allodynia in rats. KB 09 and KB 10 substantially attenuated the CCI elicited hyperalgesia and allodynia. They significantly reduced the biomarkers of pain and inflammation like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ELISA and while enhanced the GSH, SOD and CAT and diminished the MDA levels during antioxidant assays. KB 09 displayed -9.62 kcal/mol with TNF-α and -7.68 kcal/mol binding energy with IL-6 whereas KB 10 exhibited binding energy of -8.20 kcal/mol with IL-6 while -11.68 kcal/mol with TNF-α and hence both trial compounds ensured stable interaction with IL-6 and TNF-α during computational analysis. The results advocated that both methanimine derivatives might be novel candidates for attenuation of CCI-induced neuropathic pain prospects via anti-nociceptive, anti-inflammatory and antioxidant mechanisms.

Intranasal Administration of Apelin-13 Ameliorates Cognitive Deficit in Streptozotocin-Induced Alzheimer's Disease Model via Enhancement of Nrf2-HO1 Pathways.

The discovery of novel diagnostic methods and therapies for Alzheimer's disease (AD) faces significant challenges. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate Apelin-13's mechanism of action in an in vivo model of AD induced by streptozocin (STZ). We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests, primarily, behavioral assessment, histological analysis, and biochemical assays, in order to evaluate synaptic plasticity and oxidative stress signaling pathways. Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated by the enhancement of synaptic plasticity and the attenuation of oxidative stress signaling pathways. The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

Optogenetic behavioral studies in depression research: A systematic review

Optogenetics has made substantial contributions to our understanding of the mechanistic underpinnings of depression. This systematic review employs quantitative analysis to investigate the impact of optogenetic stimulation in mice and rats on behavioral alterations in social interaction, sucrose consumption, and mobility. The review analyses optogenetic behavioral studies using standardized behavioral tests to detect behavioral changes induced via optogenetic stimulation in stressed or stress-naive mice and rats. Behavioral changes were evaluated as either positive, negative, or not effective. The analysis comprises the outcomes of 248 behavioral tests of 168 studies described in 37 articles, including negative and null results. Test outcomes were compared for each behavior, depending on the animal cohort, applied type of stimulation and the stimulated neuronal circuit and cell type. The presented synthesis contributes toward a comprehensive picture of optogenetic behavioral research in the context of depression.

Development and characterization of an automated behavioral assessment platform for the Göttingen minipig

The Göttingen minipig is fast becoming the standard for assessing dermal chemical hazards because, like most swine, its skin is predictive of human skin response and because this strain’s smaller size makes laboratory manipulations and husbandry easier. Unfortunately, standard behavioral tests and apparatus have not been developed for behavioral assessments of this swine strain. Indeed, computer-controlled automated behavioral testing procedures are much needed. The present research advanced this goal by producing a home-cage behavioral testing system that could accommodate minipigs of various sizes (ages). An aluminum frame housed three levers for recording operant responses, and LEDs above and below each lever served as discriminative stimuli. A commercially available food pellet dispenser was attached to a specialized pellet receptacle capable of measuring pellet retrieval. Two behavioral tests were selected and adapted from our commonly used non-human primate behavioral assessments: delayed match-to-sample (a memory test) and temporal response differentiation (a time-estimation test). Minipigs were capable of learning both tests and attaining stable performance. Next, scopolamine was used to validate the sensitivity of the behavioral tests for gauging behavioral perturbations in this swine strain. Scopolamine dose-effect functions were comparable to those observed in other species, including non-human primates, wherein 37.5 µg/kg of scopolamine (administered intramuscularly) reduced responding approximately 50%. Thus, we were successful in developing the apparatus and automated operant behavioral tests necessary to characterize drug safety in this swine strain. This capability will be valuable for characterizing chemical agent toxicity as well as the safety and efficacy of medical countermeasures.

Domoic acid affects brain morphology and causes behavioral alterations in two fish species

Domoic acid (DA) produces neurotoxic damage in seabirds and marine mammals when they are exposed to this potent neurotoxin. Other vertebrates are also susceptible to DA intoxication including humans. However, neurobehavioral affectations have not been detected in fish when naturally exposed to DA but only when it is administered intraperitoneally. Therefore, the current idea is that fish are less sensitive to DA acquired under ecologically relevant routes of exposure. Here, we show that oral consumption of DA induces neurobehavioral and histopathological alterations in the brain and heart of totoaba (Totoaba macdonaldi) and striped bass (Morone saxatilis). Lesions were found in both species in the optic tectum and cerebellum after exposure for 7 days to a diet containing 0.776 µgDA g−1. The affectations prevailed chronically. Also, we found that cardiac tissue exhibits lesions and focal atrium melanism. Although affectations of the brain and heart tissue were evident, excitotoxic signs like those described for other vertebrates were not observed. However, the use of standardized behavioral tests (dark/light and antipredator avoidance tests) permitted the detection of behavioral impairment of fish after DA exposure. Pathological and associated behavioral alterations produced by DA can have relevant physiological consequences but also important ecological implications.

Social contact from birth influences personality traits of group-housed dairy calves

The objective of this study was to assess effects of prior social contact on the expression of personality traits in group-housed calves. Holstein heifer and bull calves were housed in either individual pens (n = 16), or in pairs (n = 8 pairs) at birth before they were mingled between treatments and moved to group pens at approximately 2 wk of life (8 calves/pen). During wk 4 of life, calves were tested in a series of standardized behavioral tests: an open field test, a novel object test, an unfamiliar calf test, and an unfamiliar human test. Responses in the open field test and novel object test were analyzed using principal component analysis, yielding 2 factors interpreted as bold and inactive/grooming. Calves housed in pairs before grouping had greater scores for bold and tended to have lower scores for inactive/grooming. Responses in the unfamiliar calf and human tests were similarly analyzed, yielding 3 factors interpreted as calf-directed, active, and human-directed. Calves housed in pairs before grouping had lower scores for calf-directed, tended to have lower scores for active, and scores for human-directed did not differ. Following grouping, average daily gain, milk replacer intake, and meal frequency did not differ between previous housing treatments. Our results suggest that behavioral traits reflective of personality in group-housed calves may be influenced by social contact from birth even following adaptation to group-housing.

Disparate behavioral types in wild and reared juveniles of gilthead seabream

Fish differ consistently in behavior within the same species and population, reflecting distinct behavioral types (BTs). Comparing the behavior of wild and reared individuals provides an excellent opportunity to delve into the ecological and evolutionary consequences of BTs. In this work, we evaluated the behavioral variation of wild and reared juvenile gilthead seabreams, Sparus aurata, a highly relevant species for aquaculture and fisheries. We quantified behavioral variation along the five major axes of fish behavioral traits (exploration-avoidance, aggressiveness, sociability, shyness-boldness, and activity) using standardized behavioral tests and a deep learning tracking algorithm for behavioral annotation. Results revealed significant repeatability in all five behavior traits, suggesting high consistency of individual behavioral variation across the different axes in this species. We found reared fish to be more aggressive, social and active compared to their wild conspecifics. Reared individuals also presented less variance in their aggressiveness, lacking very aggressive and very tame individuals. Phenotypic correlation decomposition between behavioral types revealed two different behavioral syndromes: exploration-sociability and exploration-activity. Our work establishes the first baseline of repeatability scores in wild and reared gilthead seabreams, providing novel insight into the behavior of this important commercial species with implications for fisheries and aquaculture.

Self-Conducted and Skype-Mediated Exposure Therapy for a Severe Balloon Phobia: A Single-Case Design

Real-life exposure therapy involving Skype technology was used to successfully treat a 27-year-old woman with a debilitating fear of balloons. The majority of the therapeutic work consisted of self-conducted exposure by the client, augmented by two hours of therapist-modeled and guided exposure to blowing up and popping balloons, observed by the client via Skype and then emulated with therapist guidance. This case study was jointly documented by the client, a licensed clinical social worker (LCSW) and psychotherapist, and the therapist, also an LCSW as well as a board-certified behavior analyst. Apart from the client???s personal narrative, the outcomes of the case study were supported by two standardized behavioral approach tests conducted by the therapist prior to treatment and after three months of treatment. A novel aspect of this treatment was the use of Skype technology to make possible real-life exposure therapy conducted by the therapist and synchronously delivered to the client, who was more than 200 miles distant. The joint writing of first person perspectives of treatment by the client and therapist is another unusual element that we believe strengthens the credibility of this single-case study.

Vertigoheel promotes rodent cognitive performance in multiple memory tests.

Cognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04's biological activity. In the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus. Administration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain. Our findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

Hierarchical psychophysiological pathways subtend perceptual asymmetries in Neglect

Stroke patients with left Hemispatial Neglect (LHN) show deficits in perceiving left contralesional stimuli with biased visuospatial perception towards the right hemifield. However, very little is known about the functional organization of the visuospatial perceptual neural network and how this can account for the profound reorganization of space representation in LHN.In the present work, we aimed at (1) identifying EEG measures that discriminate LHN patients against controls and (2) devise a causative neurophysiological model between the discriminative EEG measures. To these aims, EEG was recorded during exposure to lateralized visual stimuli which allowed for pre-and post-stimulus activity investigation across three groups: LHN patients, lesioned controls, and healthy individuals. Moreover, all participants performed a standard behavioral test assessing the perceptual asymmetry index in detecting lateralized stimuli. The between-groups discriminative EEG patterns were entered into a Structural Equation Model for the identification of causative hierarchical associations (i.e., pathways) between EEG measures and the perceptual asymmetry index.The model identified two pathways. A first pathway showed that the combined contribution of pre-stimulus frontoparietal connectivity and individual-alpha-frequency predicts post-stimulus processing, as measured by visual-evoked N100, which, in turn, predicts the perceptual asymmetry index. A second pathway directly links the inter-hemispheric distribution of alpha-amplitude with the perceptual asymmetry index. The two pathways can collectively explain 83.1% of the variance in the perceptual asymmetry index.Using causative modeling, the present study identified how psychophysiological correlates of visuospatial perception are organized and predict the degree of behavioral asymmetry in LHN patients and controls.

Curcumin Ameliorates Neurobehavioral Deficits in Ambient Dusty Particulate Matter-Exposure Rats: The Role of Oxidative Stress.

It has been consistently found that exposure to ambient air pollution, such as particulate matter (PM), results in cognitive impairments and mental disorders. This study aimed to investigate the possible neuroprotective effects of curcumin, a polyphenol compound, on the neurobehavioral deficits and to identify the role of oxidative stress in dusty PM exposure rats. Rats received curcumin (50mg/kg, daily, gavage, 2weeks) 30min before placing animals in a clean air chamber (≤ 150µg/m3, 60min daily, 2weeks) or ambient dusty PM chamber (2000-8000µg/m3, 60min daily, 2weeks). Subsequently, the cognitive and non-cognitive functions of the animals were evaluated using standard behavioral tests. Moreover, blood-brain barrier (BBB) permeability, brain water content (BWC), oxidative-antioxidative status, and histological changes were determined in the cerebral cortex and hippocampal areas of the rats. Our results showed that curcumin administration in dusty PM exposure rats attenuates memory impairment, decreases anxiety-/depression-like behaviors, and improves locomotor/exploratory activities. These findings were accompanied by reduced BBB permeability and BWC, decreasing oxidative stress, and lessening neuronal loss in the cerebral cortex and different hippocampal areas. The results of this study suggest that curcumin's antioxidant properties may contribute to its efficacy in improving neurobehavioral deficits and preventing neuronal loss associated with dusty PM exposure.

Cancer treatment induces neuroinflammation and behavioral deficits in mice.

Introduction: Cancer survivors are increasingly diagnosed with a syndrome of neurocognitive dysfunction termed cancer-related cognitive impairment (CRCI). Chemotherapy and radiation therapy have been implicated in CRCI; however, its underlying pathogenesis remains unclear, hindering effective prevention or treatment. Methods: We used the hairless strain SKH1 (11-12-week-old) and treated the mice with radiation to the right hindlimb, doxorubicin (a chemotherapy agent), concurrent radiation, and doxorubicin, or no treatment (control). Neurocognition was evaluated via standardized behavioral testing following treatment. Mice were subsequently humanely euthanized, and plasma and brains were collected to identify inflammatory changes. Results: Mice treated with radiation, doxorubicin, or both radiation and doxorubicin demonstrated equivalent hippocampal dependent memory deficits and significant increases in activated microglia and astrocytes compared to control mice. Doxorubicin-treated mice had significantly increased plasma IL-6 and failed to gain weight compared to control mice over the study period. Discussion: This study demonstrates that non-brain directed radiation induces both gliosis and neurocognitive deficits. Moreover, this work presents the first characterization of SKH1 mice as a relevant and facile animal model of CRCI. This study provides a platform from which to build further studies to identify potential key targets that contribute to CRCI such that strategies can be developed to mitigate unintended neuropathologic consequences associated with anticancer treatment.

Redox intensity and psychoemotional status of rats in burn skin injury

Relevance. Currently, the problem of regeneration of damaged skin, including of a burn nature, remains relevant. The work describes the results of the study of the redox intensity and of the psychoemotional status of rats in thermal skin injury. The aim of the study is an experimental study of the redox intensity and of the psychoemotional status of rats in burn skin injury. Materials and Methods. The study was conducted on nonlinear male rats of average weight 250 grams for 6-8 months. To assess psychoemotional status, studies were carried out using standard psychophysiological methods: «Open Field», «Elevated cruciform maze», «Suok Test» and «Porsolt.» The intensity of redox processes in the hypothalamic and prefrontal regions of the brain was assessed by determining the intensity of lipid peroxidation and catalase activity. The activity of lipid peroxidation was determined by the initial content of malonic dialdehyde, as well as by the rate of spontaneous and ascorbic peroxidation of lipids. Results and Discussion. During the study, it was found that burn damage to the skin was accompanied by an increase in the concentration of TBC-active products of lipid peroxidation in the hypothalamic and prefrontal regions of the brain of rats, which resulted in the development of oxidative stress. Burn injury initiated peroxidation processes in the studied areas of the brain, the most pronounced in the early period of the burn process (on days 2-4), with varying degrees decreasing in the following periods (on days 7, 10). The results of the assessment of the psychoemotional status of animals in burn skin injury in standard behavioral tests confirm the involvement of the nervous system in response to stress, the reflex activity of which under stressful conditions manifests itself in a change in behavioral reactions. In the conditions of burn damage to the skin, signs of an alarming-depressive state, in particular disorientation in space, suppression of the psychoemotional state, and a change in the nature of behavioral reactions were noted. Conclusion. Thus, the revealed changes in the intensity of redox processes and the peculiarities of the psychoemotional status of rats in burn skin damage are the result of biochemical and functional disorders of the brain, activated during protective and adaptation reactions in burn injury.

Preclinical Model to Evaluate Outcomes of Amyloid Cross-Toxicity in the Rodent Brain.

The progress of neurodegenerative disorders correlates with the spread of their associated amyloidogenic proteins. Here, we investigated whether amyloid entry into nonconstitutive neurons could drive cross-toxic outcomes. Amyloid β (Aβ) was stereotaxically introduced into the rodent midbrain tegmentum, where it is not endogenously expressed. Postinfusion, rodent motor and sensorimotor capacities were assessed by standard behavioral tests at 3, 6, 9, and 12 months. The longitudinal study revealed no behavioral abnormalities. However, Aβ insult provoked intraneuronal inclusions positive for phosphorylated α-synuclein in dopaminergic neurons and were seen throughout the midbrain, a pathognomonic biomarker suggesting Parkinson's pathogenesis. These findings not only underscore the cross-toxic potential of amyloid proteins but also provide a mechanism by which they disrupt homeostasis in nonconstitutive neurons and cause neuronal corruption, injury, and demise. This study may help reconcile the large incidence of neurodegenerative comorbidity observed clinically.